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TitleDynamical modeling of liver Aquaporin-9 expression and glycerol permeability in hepatic glucose metabolism
AbstractLiver is crucial in the homeostasis of glycerol, an important metabolic intermediate. Plasma glycerol is imported by hepatocytes mainly through Aquaporin-9 (AQP9), an aquaglyceroporin channel negatively regulated by insulin in rodents. AQP9 is of critical importance in glycerol metabolism since hepatic glycerol utilization is rate-limited at the hepatocyte membrane permeation step. Glycerol kinase catalyzes the initial step for the conversion of the imported glycerol into glycerol-3-phosphate, a major substrate for de novo synthesis of glucose (gluconeogenesis) and/or triacyglycerols (lipogenesis). A model addressing the glucose-insulin system to describe the hepatic glycerol import and metabolism and the correlation with the glucose homeostasis is lacking so far. Here we consider a system of first-order ordinary differential equations delineating the relevance of hepatocyte AQP9 in liver glycerol permeability. Assuming the hepatic glycerol permeability as depending on the protein levels of AQP9, a mathematical function is designed describing the time course of the involvement of AQP9 in mouse hepatic glycerol metabolism in different nutritional states. The resulting theoretical relationship is derived fitting experimental data obtained with murine models at the fed, fasted or re-fed condition. While providing useful insights into the dynamics of liver AQP9 involvement in male rodent glycerol homeostasis our model may be adapted to the human liver serving as an important module of a whole body-model of the glucose metabolism both in health and metabolic diseases.
SourceEuropean journal of cell biology (Print) 96, pp. 61–69
KeywordsDifferential equations
JournalEuropean journal of cell biology (Print)
EditorElsevier, Urban u. Fischer, München, Germania
Year2017
TypeArticolo in rivista
DOI10.1016/j.ejcb.2016.12.003
AuthorsGena P.; Del Buono N.; D'Abbicco M.; Mastrodonato M.; Berardi M.; Svelto M.; Lopez L.; Calamita G.
Text379337 2017 10.1016/j.ejcb.2016.12.003 Scopus 2 s2.0 85009063802 Differential equations Dynamical modeling of liver Aquaporin 9 expression and glycerol permeability in hepatic glucose metabolism Gena P.; Del Buono N.; D Abbicco M.; Mastrodonato M.; Berardi M.; Svelto M.; Lopez L.; Calamita G. Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Universita degli Studi di Bari Aldo Moro , via Orabona, Bari, 4 70125, Italy; Dipartimento di Matematica, Universita degli Studi di Bari Aldo Moro , via Orabona, Bari, 4 70125, Italy; Dipartimento di Biologia, Universita degli Studi di Bari Aldo Moro , via Orabona, Bari, 4 70125, Italy; Istituto di Ricerca sulle Acque, Consiglio Nazionale delle Ricerche CNR , via De Blasio, Bari, 5 70132, Italy Liver is crucial in the homeostasis of glycerol, an important metabolic intermediate. Plasma glycerol is imported by hepatocytes mainly through Aquaporin 9 AQP9 , an aquaglyceroporin channel negatively regulated by insulin in rodents. AQP9 is of critical importance in glycerol metabolism since hepatic glycerol utilization is rate limited at the hepatocyte membrane permeation step. Glycerol kinase catalyzes the initial step for the conversion of the imported glycerol into glycerol 3 phosphate, a major substrate for de novo synthesis of glucose gluconeogenesis and/or triacyglycerols lipogenesis . A model addressing the glucose insulin system to describe the hepatic glycerol import and metabolism and the correlation with the glucose homeostasis is lacking so far. Here we consider a system of first order ordinary differential equations delineating the relevance of hepatocyte AQP9 in liver glycerol permeability. Assuming the hepatic glycerol permeability as depending on the protein levels of AQP9, a mathematical function is designed describing the time course of the involvement of AQP9 in mouse hepatic glycerol metabolism in different nutritional states. The resulting theoretical relationship is derived fitting experimental data obtained with murine models at the fed, fasted or re fed condition. While providing useful insights into the dynamics of liver AQP9 involvement in male rodent glycerol homeostasis our model may be adapted to the human liver serving as an important module of a whole body model of the glucose metabolism both in health and metabolic diseases. 96 Published version http //www.scopus.com/record/display.url eid=2 s2.0 85009063802 origin=inward Articolo in rivista Elsevier, Urban u. Fischer 0171 9335 European journal of cell biology Print European journal of cell biology Print Eur. j. cell biol. Print European journal of cell biology. Print EJCB. European journal of cell biology Print Print marco.berardi BERARDI MARCO