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Model-Based Quantification of the Systemic Interplay between Glucose and Fatty Acids in the Postprandial State
Eindhoven University of Technology, Netherlands.
Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. CVMD iMED DMPK AstraZeneca RandD, Sweden.
University of Gothenburg, Sweden.
Eindhoven University of Technology, Netherlands.
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, e0135665- p.Article in journal (Refereed) Published
Abstract [en]

In metabolic diseases such as Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, the systemic regulation of postprandial metabolite concentrations is disturbed. To understand this dysregulation, a quantitative and temporal understanding of systemic postprandial metabolite handling is needed. Of particular interest is the intertwined regulation of glucose and non-esterified fatty acids (NEFA), due to the association between disturbed NEFA metabolism and insulin resistance. However, postprandial glucose metabolism is characterized by a dynamic interplay of simultaneously responding regulatory mechanisms, which have proven difficult to measure directly. Therefore, we propose a mathematical modelling approach to untangle the systemic interplay between glucose and NEFA in the postprandial period. The developed model integrates data of both the perturbation of glucose metabolism by NEFA as measured under clamp conditions, and postprandial time-series of glucose, insulin, and NEFA. The model can describe independent data not used for fitting, and perturbations of NEFA metabolism result in an increased insulin, but not glucose, response, demonstrating that glucose homeostasis is maintained. Finally, the model is used to show that NEFA may mediate up to 30-45% of the postprandial increase in insulin-dependent glucose uptake at two hours after a glucose meal. In conclusion, the presented model can quantify the systemic interactions of glucose and NEFA in the postprandial state, and may therefore provide a new method to evaluate the disturbance of this interplay in metabolic disease.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE , 2015. Vol. 10, no 9, e0135665- p.
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-121744DOI: 10.1371/journal.pone.0135665ISI: 000360965800006PubMedID: 26356502OAI: diva2:859361

Funding Agencies|European Union [305707]; Linkoping Initiative within Life Science Technologies; Ostergotland County Council; Swedish Research Council; AstraZeneca

Available from: 2015-10-06 Created: 2015-10-05 Last updated: 2016-04-24

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