title: Model-Based Quantification of the Systemic Interplay between Glucose and Fatty Acids in the Postprandial State.
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.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands.
authors.forename: Fianne L P
authors.initials: FL
authors.lastname: Sips
authors.affiliation: Department of Biomedical Engineering, Linköping University, SE-58185, Linköping, Sweden; CVMD iMED DMPK AstraZeneca R&D, 431 83, Mölndal, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Nyman
authors.affiliation: Health Metrics at Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Adiels
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands.
authors.forename: Peter A J
authors.initials: PA
authors.lastname: Hilbers
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, SE-58185, Linköping, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Strålfors
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands.
authors.forename: Natal A W
authors.initials: NA
authors.lastname: van Riel
authors.affiliation: Department of Biomedical Engineering, Linköping University, SE-58185, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, SE-58185, Linköping, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Cedersund
mesh_terms: D000284:Administration, Oral; D002138:Calibration; D003198:Computer Simulation; D019992:Databases as Topic; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006706:Homeostasis; D006801:Humans; D007332:Insulin Infusion Systems; D007700:Kinetics; D008954:Models, Biological; D019518:Postprandial Period
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D005947:Glucose