Multiscale modeling of acute insulin resistance in critical care
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KeywordsInsulin Resistance Insulin Sensitivity Insulin Signaling Insulin Receptor Substrate Multiscale Model
Stress hyperglycemia in the critically ill is a complex process in which insulin signaling is systematically hijacked to provide energy substrate for metabolic priorities such as cell healing or infection containment. Fluctuating levels of plasma glucose are associated with increased mortality in the ICU . We develop a multiscale mathematical model that can characterize the severity of stress hyperglycemia based on a fundamental understanding of the signaling molecules involved.
Insulin resistance following insult has been shown to be driven primarily by the immune response via the cytokine IL-6 . We created a multiscale mathematical model that links circulating glucose and insulin concentration dynamics from the extended minimal model  to a cellular insulin response model  that captures insulin-mediated glucose uptake in an insulin-responsive cell.
A multiscale model has been developed to describe the inhibitory effects of IL-6 on insulin-mediated glucose uptake. Cellular inhibitory dynamics were shown to capture reduced insulin sensitivity on the macroscale, which could then be used to characterize insulin sensitivity and to provide insulin treatment advice to reduce glucose variability.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.