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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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Detalles Bibliográficos
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:
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
Descripción
Sumario: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.