A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism

We present a mathematical model of key glucose metabolic pathways in two cells of the human retina: the rods and the retinal pigmented epithelium (RPE). Computational simulations of glucose transporter 1 (GLUT1) inhibition in the model accurately reproduce experimental data from conditional knockout...

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Autores principales: Aparicio, Andrea, Camacho, Erika T., Philp, Nancy J., Wirkus, Stephen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226191/
https://www.ncbi.nlm.nih.gov/pubmed/35739198
http://dx.doi.org/10.1038/s41598-022-13950-3
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author Aparicio, Andrea
Camacho, Erika T.
Philp, Nancy J.
Wirkus, Stephen A.
author_facet Aparicio, Andrea
Camacho, Erika T.
Philp, Nancy J.
Wirkus, Stephen A.
author_sort Aparicio, Andrea
collection PubMed
description We present a mathematical model of key glucose metabolic pathways in two cells of the human retina: the rods and the retinal pigmented epithelium (RPE). Computational simulations of glucose transporter 1 (GLUT1) inhibition in the model accurately reproduce experimental data from conditional knockout mice and reveal that modification of GLUT1 expression levels of both cells differentially impacts their metabolism. We hypothesize that, under glucose scarcity, the RPE’s energy producing pathways are altered in order to preserve its functionality, impacting the photoreceptors’ outer segment renewal. On the other hand, when glucose is limited in the rods, aerobic glycolysis is preserved, which maintains the lactate contribution to the RPE.
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spelling pubmed-92261912022-06-25 A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism Aparicio, Andrea Camacho, Erika T. Philp, Nancy J. Wirkus, Stephen A. Sci Rep Article We present a mathematical model of key glucose metabolic pathways in two cells of the human retina: the rods and the retinal pigmented epithelium (RPE). Computational simulations of glucose transporter 1 (GLUT1) inhibition in the model accurately reproduce experimental data from conditional knockout mice and reveal that modification of GLUT1 expression levels of both cells differentially impacts their metabolism. We hypothesize that, under glucose scarcity, the RPE’s energy producing pathways are altered in order to preserve its functionality, impacting the photoreceptors’ outer segment renewal. On the other hand, when glucose is limited in the rods, aerobic glycolysis is preserved, which maintains the lactate contribution to the RPE. Nature Publishing Group UK 2022-06-23 /pmc/articles/PMC9226191/ /pubmed/35739198 http://dx.doi.org/10.1038/s41598-022-13950-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Aparicio, Andrea
Camacho, Erika T.
Philp, Nancy J.
Wirkus, Stephen A.
A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism
title A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism
title_full A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism
title_fullStr A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism
title_full_unstemmed A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism
title_short A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism
title_sort mathematical model of glut1 modulation in rods and rpe and its differential impact in cell metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226191/
https://www.ncbi.nlm.nih.gov/pubmed/35739198
http://dx.doi.org/10.1038/s41598-022-13950-3
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