2024
Félix-Martínez, Gerardo J.; Osorio-Londoño, Diana María; Godínez-Fernández, J. Rafael
In: PLOS Computational Biology, vol. 20, iss. 8, pp. e1012357, 2024, ISSN: 1553-7358.
@article{nokey,
title = {Impact of oxygen and glucose availability on the viability and connectivity of islet cells: A computational study of reconstructed avascular human islets},
author = {Gerardo J. Félix-Martínez and Diana María Osorio-Londoño and J. Rafael Godínez-Fernández},
url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1012357},
doi = {10.1371/journal.pcbi.1012357},
issn = {1553-7358},
year = {2024},
date = {2024-08-08},
urldate = {2024-08-08},
journal = {PLOS Computational Biology},
volume = {20},
issue = {8},
pages = {e1012357},
abstract = {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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2023
Félix-Martínez, Gerardo J.; Picones, Arturo; Godínez-Fernández, J. Rafael
Short and long-range correlations in single-channel currents from inwardly rectifying K channels Journal Article
In: Chaos, Solitons & Fractals , vol. 178, pp. 114333, 2023, ISSN: 1873-2887.
@article{nokey,
title = {Short and long-range correlations in single-channel currents from inwardly rectifying K channels},
author = {Gerardo J. Félix-Martínez and Arturo Picones and J. Rafael Godínez-Fernández},
url = {https://www.sciencedirect.com/science/article/abs/pii/S0960077923012353},
doi = {10.1016/j.chaos.2023.114333},
issn = { 1873-2887},
year = {2023},
date = {2023-12-15},
urldate = {2023-12-15},
journal = {Chaos, Solitons & Fractals },
volume = {178},
pages = {114333},
abstract = {Ion channels mediate the transport of ions through the cell membrane and are involved in key processes such as muscle contraction, nerve excitability and hormone secretion. For decades, the main focus of the standard techniques for the analysis and modeling of single-channel currents has been to characterize the gating of ionic channels by analyzing the current amplitudes and dwell-time histograms, thus neglecting the possibility that pore fluctuations (open and closed), usually considered to be stochastic noise, might contain valuable information about the functional aspects of ion channels. Based on the analysis of a deterministic model indicating that the stochastic gating of ion channels could be produced by correlated pore fluctuations, in this work, we analyzed experimental recordings of single channel currents of an inwardly rectifying K channel in order to demonstrate the presence of both short and long range correlations in the open and closed pore fluctuations},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Félix-Martínez, Gerardo J.; Godínez-Fernández, J. Rafael
A primer on modelling pancreatic islets: from models of coupled β-cells to multicellular islet models Journal Article
In: Islets, vol. 15, iss. 1, 2023, ISSN: 1938-2022.
@article{nokey,
title = {A primer on modelling pancreatic islets: from models of coupled β-cells to multicellular islet models},
author = {Gerardo J. Félix-Martínez and J. Rafael Godínez-Fernández},
url = {https://www.tandfonline.com/doi/full/10.1080/19382014.2023.2231609?src=},
doi = {10.1080/19382014.2023.2231609},
issn = {1938-2022},
year = {2023},
date = {2023-07-07},
urldate = {2023-07-07},
journal = {Islets},
volume = {15},
issue = {1},
abstract = {Pancreatic islets are mini-organs composed of hundreds or thousands of ɑ, β and δ-cells, which, respectively, secrete glucagon, insulin and somatostatin, key hormones for the regulation of blood glucose. In pancreatic islets, hormone secretion is tightly regulated by both internal and external mechanisms, including electrical communication and paracrine signaling between islet cells. Given its complexity, the experimental study of pancreatic islets has been complemented with computational modeling as a tool to gain a better understanding about how all the mechanisms involved at different levels of organization interact. In this review, we describe how multicellular models of pancreatic cells have evolved from the early models of electrically coupled β-cells to models in which experimentally derived architectures and both electrical and paracrine signals have been considered.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Godínez-Fernández, J. Rafael; Félix-Martínez, Gerardo J.
Papel de los canales iónicos de la membrana celular en la respuesta inmune Journal Article
In: Contactos, Revista de Educación en Ciencias e Ingeniería, vol. 129, 2023.
@article{nokey,
title = {Papel de los canales iónicos de la membrana celular en la respuesta inmune},
author = {J. Rafael Godínez-Fernández and Gerardo J. Félix-Martínez},
url = {https://contactos.izt.uam.mx/index.php/contactos/article/view/282},
year = {2023},
date = {2023-06-01},
urldate = {2023-06-01},
journal = {Contactos, Revista de Educación en Ciencias e Ingeniería},
volume = {129},
abstract = {Los canales iónicos son proteinas de membrana ubicuas, clave para una gran variedad de procesos fisiológicos que involucran células excitables y no excitables. Mientas que el papel de los canales iónicos en las propiedades funcionales de las células excitables ha sido conocido por décadas, el estudio de su participación en la actividad de células no excitables ha sido hasta cierto punto relegado. Este es el caso de las células inmunes, como los linfocitos B y T, cuya viabilidad y regulación durante la respuesta inmune depende en gran medida en la actividad de los canales iónicos. En este artículo describimos de manera general la importancia de los canales iónicos para la respuesta inmune, las técnicas experimentales utilizadas para su estudio, los procesos celulares involucrados, y cómo se ven alterados en escenarios patológicos como la inmunodeficiencia adquirida por desnutrición.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Félix-Martínez, Gerardo J.; Godínez-Fernández, J. Rafael
Islotes pancreáticos y su papel en la regulación de la glucosa Journal Article
In: Contactos, Revista de Educación en Ciencias e Ingeniería, vol. 128, 2023.
@article{nokey,
title = {Islotes pancreáticos y su papel en la regulación de la glucosa},
author = {Gerardo J. Félix-Martínez and J. Rafael Godínez-Fernández},
url = {https://contactos.izt.uam.mx/index.php/contactos/article/view/274},
year = {2023},
date = {2023-04-10},
urldate = {2023-04-10},
journal = {Contactos, Revista de Educación en Ciencias e Ingeniería},
volume = {128},
abstract = {En el cuerpo humano, los niveles de glucosa en sangre son estríctamente regulados por una gran variedad de mecanismos a diferentes niveles de organización: desde la secreción de hormonas a nivel celular en el páncreas, hasta llegar a sus efectos a nivel sistémico, que dan lugar a un aumento o disminución de la glucosa sanguínea, según se requiera. En este artículo, describimos los mecanismos involucrados, cómo funcionan y qué pasa cuando estos fallan.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2022
Valverde-Alonzo, Crystal Azucena; Félix-Martínez, Gerardo Jorge; González-Velez, Virginia; Gil, Amparo
Role of Endogenous Ca2+ Buffering and the Readily Releasable Pool on Fast Secretion in Auditory Inner Hair Cells Proceedings Article
In: XLV Mexican Conference on Biomedical Engineering. CNIB 2022. IFMBE Proceedings, pp. 212-218, Springer Cham, 2022, ISBN: 978-3-031-18256-3.
@inproceedings{crystalsomib22,
title = {Role of Endogenous Ca2+ Buffering and the Readily Releasable Pool on Fast Secretion in Auditory Inner Hair Cells},
author = {Crystal Azucena Valverde-Alonzo and Gerardo Jorge Félix-Martínez and Virginia González-Velez and Amparo Gil},
doi = {10.1007/978-3-031-18256-3_23},
isbn = {978-3-031-18256-3},
year = {2022},
date = {2022-10-24},
urldate = {2022-10-24},
booktitle = {XLV Mexican Conference on Biomedical Engineering. CNIB 2022. IFMBE Proceedings},
volume = {86},
pages = {212-218},
publisher = {Springer Cham},
abstract = {Sensory hair cells, located at the cochlea, convert sound into a depolarizing stimulus that, as a response to an increase in the intracellular Ca2+
2
+
concentration, triggers the release of glutamate. Experimental observations have shown that depending on their location in the inner ear, sensory hair cells respond differently to sounds of different frequencies. The origin of this behavior is still a matter of debate but, given the importance of the dynamics of intracellular Ca2+
2
+
for the exocytotic response, it has been hypothesized that the availability of endogenous Ca2+
2
+
buffers at the active zone, along with the size of the readily releasable pool of glutamate vesicles, could be associated to the frequency-dependent tuning of the exocytotic response. Here, we implemented a computational model of the active zone of a sensory hair cell with the main objective of evaluating the effects of the endogenous Ca2+
2
+
buffers and the readily releasable pool on the fast exocytosis of glutamate.},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
2
+
concentration, triggers the release of glutamate. Experimental observations have shown that depending on their location in the inner ear, sensory hair cells respond differently to sounds of different frequencies. The origin of this behavior is still a matter of debate but, given the importance of the dynamics of intracellular Ca2+
2
+
for the exocytotic response, it has been hypothesized that the availability of endogenous Ca2+
2
+
buffers at the active zone, along with the size of the readily releasable pool of glutamate vesicles, could be associated to the frequency-dependent tuning of the exocytotic response. Here, we implemented a computational model of the active zone of a sensory hair cell with the main objective of evaluating the effects of the endogenous Ca2+
2
+
buffers and the readily releasable pool on the fast exocytosis of glutamate.
Flores-Santillán, Diego; Godínez-Fernández, José Rafael; Martínez, Gerardo Jorge Félix
Effects of Blood Flow on Insulin Concentration: A Modelling Study Proceedings Article
In: XLV Mexican Conference on Biomedical Engineering. CNIB 2022. IFMBE Proceedings, pp. 219-224, Springer Cham, 2022, ISBN: 978-3-031-18256-3.
@inproceedings{diegocnib22,
title = {Effects of Blood Flow on Insulin Concentration: A Modelling Study},
author = {Diego Flores-Santillán and José Rafael Godínez-Fernández and Gerardo Jorge Félix Martínez},
doi = {10.1007/978-3-031-18256-3_24},
isbn = {978-3-031-18256-3},
year = {2022},
date = {2022-10-24},
urldate = {2022-10-24},
booktitle = {XLV Mexican Conference on Biomedical Engineering. CNIB 2022. IFMBE Proceedings},
volume = {86},
pages = {219-224},
publisher = {Springer Cham},
abstract = {Pancreatic islets are highly vascularized micro-organs composed of glucagon-secreting α-cells, insulin-secreting β-cells and somatostatin-secreting δ-cells. Within the islets, the exchange of nutrients and hormones, as well as paracrine communication between islet cells, rely on a dense network of capillaries that allows the pancreatic hormones to travel throughout the islet before reaching the systemic circulation. Based on experimental observations, three models for islet vasculature have been proposed: pole-to-pole, center-to-periphery and periphery-to-center. However, despite its importance, the structure and functional role of the islet vasculature remains an open question. In this work, we developed computational models of the three vasculature models, aiming to evaluate the effect of the vasculature on the concentration of insulin reached within the islets. According to our results, the direction of blood flow could have a key role for the intraislet paracrine signaling by directing the hormones signals towards certain regions of the islet.},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Ruiz-Santiago, Sergio; Godínez-Fernández, José Rafael; Félix-Martínez, Gerardo Jorge
Simulating the Loss of β-cell Mass in a Human Pancreatic Islet: Structural and Functional Implications Proceedings Article
In: XLV Mexican Conference on Biomedical Engineering. CNIB 2022. IFMBE Proceedings, pp. 204-211, Springer Cham, 2022, ISBN: 978-3-031-18256-3.
@inproceedings{sergiocnib22,
title = {Simulating the Loss of β-cell Mass in a Human Pancreatic Islet: Structural and Functional Implications},
author = {Sergio Ruiz-Santiago and José Rafael Godínez-Fernández and Gerardo Jorge Félix-Martínez},
doi = {10.1007/978-3-031-18256-3_22},
isbn = {978-3-031-18256-3},
year = {2022},
date = {2022-10-24},
urldate = {2022-10-24},
booktitle = {XLV Mexican Conference on Biomedical Engineering. CNIB 2022. IFMBE Proceedings},
volume = {86},
pages = {204-211},
publisher = {Springer Cham},
abstract = {Type II diabetes (T2D) is a disorder defined by an impaired insulin secretion and insulin resistance. Throughout the progression of the disease, β-cells are lost due to the high-demanding environment produced by a prolonged hyperglycemic state. Moreover, T2D has been associated to structural alterations of the architecture of pancreatic islets, which might interfere negatively in the gap-junctional communication between β-cells. In this work, aiming to evaluate the effects of the loss of β-cell mass on connectivity metrics and on the synchronization of the cells’ electrical signals, we performed computational simulations of the network formed by β-cells in a human islet. Our results indicate that the loss of 15 and 30% of β-cells of a human islet would have a negative impact on the connectivity, integration and efficiency of the network, with a marked negative effect on the overall synchronization of the electrical signals of the islet β-cells.},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Félix-Martínez, Gerardo J.; Nicolás-Mata, Aurelio; Godínez-Fernández, J. Rafael
Computational Reconstruction of Pancreatic Islets as a Tool for Structural and Functional Analysis Journal Article
In: Journal of Visualized Experiments, vol. 181, pp. e63351, 2022.
@article{nokey,
title = {Computational Reconstruction of Pancreatic Islets as a Tool for Structural and Functional Analysis},
author = {Gerardo J. Félix-Martínez and Aurelio Nicolás-Mata and J. Rafael Godínez-Fernández},
editor = {Félix-Martínez, G. J., Nicolás-Mata, A., Godínez-Fernández, J. R. Computational Reconstruction of Pancreatic Islets as a Tool for Structural and Functional Analysis. <em>J. Vis. Exp.</em> (181), e63351, doi:10.3791/63351 (2022).},
url = {https://www.jove.com/es/t/63351/computational-reconstruction-pancreatic-islets-as-tool-for-structural},
doi = {10.3791/63351},
year = {2022},
date = {2022-03-09},
journal = {Journal of Visualized Experiments},
volume = {181},
pages = {e63351},
abstract = {Structural properties of pancreatic islets are key for the functional response of insulin, glucagon, and somatostatin-secreting cells, due to their implications in intraislet communication via electric, paracrine, and autocrine signaling. In this protocol, the three-dimensional architecture of a pancreatic islet is firstly reconstructed from experimental data using a novel computational algorithm. Next, the morphological and connectivity properties of the reconstructed islet, such as the number and percentages of the different type of cells, cellular volume, and cell-to-cell contacts, are obtained. Then, network theory is used to describe the connectivity properties of the islet through network-derived metrics such as average degree, clustering coefficient, density, diameter, and efficiency. Finally, all these properties are functionally evaluated through computational simulations using a model of coupled oscillators. Overall, here we describe a step-by-step workflow, implemented in IsletLab, a multiplatform application developed specifically for the study and simulation of pancreatic islets, to apply a novel computational methodology to characterize and analyze pancreatic islets as a complement to the experimental work.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Félix-Martínez, Gerardo J
IsletLab: an application to reconstruct and analyze islet architectures Journal Article
In: Islets, vol. 14, no. 1, pp. 36–39, 2022, ISSN: 1938-2022.
@article{pmid34875977,
title = {IsletLab: an application to reconstruct and analyze islet architectures},
author = {Gerardo J Félix-Martínez},
doi = {10.1080/19382014.2021.2008742},
issn = {1938-2022},
year = {2022},
date = {2022-01-01},
journal = {Islets},
volume = {14},
number = {1},
pages = {36--39},
abstract = {The continuous interaction between experimental and theoretical work has proven to be extremely useful for the study of pancreatic cells and, recently, of pancreatic islets. This prolific interaction relies on the capability of implementing computational models and methods to derive quantitative data for the analysis and interpretation of experimental observations. In this addendum I introduce Isletlab, a multiplatform application developed to provide the research community with a user-friendly interface for the implementation of computational algorithms for the characterization and simulation of pancreatic islets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}