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PLoS One. 2015 Sep 10;10(9):e0135665. doi: 10.1371/journal.pone.0135665. eCollection 2015.

Model-Based Quantification of the Systemic Interplay between Glucose and Fatty Acids in the Postprandial State.

Author information

1
Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands.
2
Department of Biomedical Engineering, Linköping University, SE-58185, Linköping, Sweden; CVMD iMED DMPK AstraZeneca R&D, 431 83, Mölndal, Sweden.
3
Health Metrics at Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
4
Department of Clinical and Experimental Medicine, Linköping University, SE-58185, Linköping, Sweden.
5
Department of Biomedical Engineering, Linköping University, SE-58185, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, SE-58185, Linköping, Sweden.

Abstract

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.

PMID:
26356502
PMCID:
PMC4565650
DOI:
10.1371/journal.pone.0135665
[Indexed for MEDLINE]
Free PMC Article

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