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An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow

Glucose homeostasis is the tight control of glucose in the blood. This complex control is important, due to its malfunction in serious diseases like diabetes, and not yet sufficiently understood. Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, w...

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Autores principales: Herrgårdh, Tilda, Li, Hao, Nyman, Elin, Cedersund, Gunnar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204084/
https://www.ncbi.nlm.nih.gov/pubmed/34140893
http://dx.doi.org/10.3389/fphys.2021.619254
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author Herrgårdh, Tilda
Li, Hao
Nyman, Elin
Cedersund, Gunnar
author_facet Herrgårdh, Tilda
Li, Hao
Nyman, Elin
Cedersund, Gunnar
author_sort Herrgårdh, Tilda
collection PubMed
description Glucose homeostasis is the tight control of glucose in the blood. This complex control is important, due to its malfunction in serious diseases like diabetes, and not yet sufficiently understood. Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. Over the last 10 years, this model has been used to insert new insights from the intra-cellular level into the larger whole-body perspective. However, the original cell-organ-body translation has during these years never been updated, despite several critical shortcomings, which also have not been resolved by other modeling efforts. For this reason, we here present an updated multi-level model. This model provides a more accurate sub-division of how much glucose is being taken up by the different organs. Unlike the original model, we now also account for the different dynamics seen in the different organs. The new model also incorporates the central impact of blood flow on insulin-stimulated glucose uptake. Each new improvement is clear upon visual inspection, and they are also supported by statistical tests. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. We hope that this model will serve as an improved basis for future data integration, useful for research and drug developments within diabetes.
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spelling pubmed-82040842021-06-16 An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow Herrgårdh, Tilda Li, Hao Nyman, Elin Cedersund, Gunnar Front Physiol Physiology Glucose homeostasis is the tight control of glucose in the blood. This complex control is important, due to its malfunction in serious diseases like diabetes, and not yet sufficiently understood. Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. Over the last 10 years, this model has been used to insert new insights from the intra-cellular level into the larger whole-body perspective. However, the original cell-organ-body translation has during these years never been updated, despite several critical shortcomings, which also have not been resolved by other modeling efforts. For this reason, we here present an updated multi-level model. This model provides a more accurate sub-division of how much glucose is being taken up by the different organs. Unlike the original model, we now also account for the different dynamics seen in the different organs. The new model also incorporates the central impact of blood flow on insulin-stimulated glucose uptake. Each new improvement is clear upon visual inspection, and they are also supported by statistical tests. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. We hope that this model will serve as an improved basis for future data integration, useful for research and drug developments within diabetes. Frontiers Media S.A. 2021-06-01 /pmc/articles/PMC8204084/ /pubmed/34140893 http://dx.doi.org/10.3389/fphys.2021.619254 Text en Copyright © 2021 Herrgårdh, Li, Nyman and Cedersund. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Herrgårdh, Tilda
Li, Hao
Nyman, Elin
Cedersund, Gunnar
An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow
title An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow
title_full An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow
title_fullStr An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow
title_full_unstemmed An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow
title_short An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow
title_sort updated organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204084/
https://www.ncbi.nlm.nih.gov/pubmed/34140893
http://dx.doi.org/10.3389/fphys.2021.619254
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