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

Andrea Aparicio; Erika T. Camacho; Nancy J. Philp; Stephen A. Wirkus

doi:10.1038/s41598-022-13950-3

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

Andrea Aparicio, Erika T. Camacho, Nancy J. Philp, Stephen A. Wirkus

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English (US)
Article number	10645
Journal	Scientific reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-13950-3
State	Published - Dec 2022

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title = "A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism",

abstract = "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{\textquoteright}s energy producing pathways are altered in order to preserve its functionality, impacting the photoreceptors{\textquoteright} 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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AU - Camacho, Erika T.

AU - Philp, Nancy J.

AU - Wirkus, Stephen A.

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N2 - 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.

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

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