PMID- 35077932 OWN - NLM STAT- MEDLINE DCOM- 20220317 LR - 20220317 IS - 1879-0534 (Electronic) IS - 0010-4825 (Linking) VI - 142 DP - 2022 Mar TI - Main glucose hepatic fluxes in healthy subjects predicted from a phenomenological-based model. PG - 105232 LID - S0010-4825(22)00024-5 [pii] LID - 10.1016/j.compbiomed.2022.105232 [doi] AB - BACKGROUND: The liver has a unique role in blood glucose regulation in postprandial, postabsorptive, and fasting states. In the context of diabetes technology, current maximal models of glucose homeostasis lack a proper dynamical description of main glucose-related fluxes acting over and from the liver, providing a rather simplistic estimation of key quantities as endogenous glucose production and insulin and glucagon clearance. METHODS: Using a three-phase well-established phenomenological-based semi-physical modeling (PBSM) methodology, we built a detailed physiological model of hepatic glucose metabolism, including glucose utilization, endogenous glucose production through gluconeogenesis and glycogenolysis, and insulin and glucagon clearance. Mean absolute errors (MAE) were used to assess the goodness of fit of the proposed model against the data from three different in-vivo experiments -two oral glucose tolerance tests (OGTT) and a mixed meal challenge following overnight fasting-in healthy subjects. RESULTS: Needing little parameter calibration, the proposed model predicts experimental systemic glucose mean +/- std 5.4 +/- 5.2, 7.5 +/- 6.8, and 7.5 +/- 7.5 mg/dL, in all three experiments. Low MAEs were also obtained for insulin and glucagon at the hepatic vein. CONCLUSIONS: The quantitative concordance of our model to the experimental data exhibits a potential for its use in the physiological study of glucose liver metabolism. The model structure and parameter interpretability allow the union with other semi-physical models for a better understanding of whole-body glucose homeostasis and its use in developing diabetes technology tools. CI - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Builes-Montano, Carlos E AU - Builes-Montano CE AD - Hospital Pablo Tobon Uribe, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia. Electronic address: esteban.builes@udea.edu.co. FAU - Lema-Perez, Laura AU - Lema-Perez L AD - Department of Engineering Cybernetics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: laura.l.perez@ntnu.no. FAU - Garcia-Tirado, Jose AU - Garcia-Tirado J AD - Center for Diabetes Technology, University of Virginia, Charlottesville, VA, USA. Electronic address: jg2bt@virginia.edu. FAU - Alvarez, Hernan AU - Alvarez H AD - Escuela de Procesos y Energia, Kalman Research Group, Facultad de Minas, Universidad Nacional de Colombia, Medellin, Colombia. Electronic address: hdalvare@unal.edu.co. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220114 PL - United States TA - Comput Biol Med JT - Computers in biology and medicine JID - 1250250 RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 9007-92-5 (Glucagon) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Blood Glucose/metabolism MH - *Diabetes Mellitus, Type 2 MH - Glucagon/metabolism MH - *Glucose/metabolism MH - Healthy Volunteers MH - Humans MH - Insulin/metabolism MH - Liver/metabolism OTO - NOTNLM OT - Diabetes mellitus OT - Glucose metabolism OT - Liver OT - Mathematical model EDAT- 2022/01/26 06:00 MHDA- 2022/03/18 06:00 CRDT- 2022/01/25 20:13 PHST- 2021/09/21 00:00 [received] PHST- 2022/01/08 00:00 [revised] PHST- 2022/01/09 00:00 [accepted] PHST- 2022/01/26 06:00 [pubmed] PHST- 2022/03/18 06:00 [medline] PHST- 2022/01/25 20:13 [entrez] AID - S0010-4825(22)00024-5 [pii] AID - 10.1016/j.compbiomed.2022.105232 [doi] PST - ppublish SO - Comput Biol Med. 2022 Mar;142:105232. doi: 10.1016/j.compbiomed.2022.105232. Epub 2022 Jan 14.