title: Dynamical modeling of liver Aquaporin-9 expression and glycerol permeability in hepatic glucose metabolism.
abstract: 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.
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari "Aldo Moro", via Orabona, 4-70125 Bari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gena
authors.affiliation: Dipartimento di Matematica, Università degli Studi di Bari "Aldo Moro", via Orabona, 4-70125 Bari, Italy.
authors.forename: Nicoletta Del
authors.initials: ND
authors.lastname: Buono
authors.affiliation: Dipartimento di Matematica, Università degli Studi di Bari "Aldo Moro", via Orabona, 4-70125 Bari, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Abbicco
authors.affiliation: Dipartimento di Biologia, Università degli Studi di Bari "Aldo Moro", via Orabona, 4-70125 Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Mastrodonato
authors.affiliation: Istituto di Ricerca sulle Acque, Consiglio Nazionale delle Ricerche (CNR), via De Blasio, 5-70132 Bari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Berardi
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari "Aldo Moro", via Orabona, 4-70125 Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Svelto
authors.affiliation: Dipartimento di Matematica, Università degli Studi di Bari "Aldo Moro", via Orabona, 4-70125 Bari, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Lopez
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari "Aldo Moro", via Orabona, 4-70125 Bari, Italy. Electronic address: giuseppe.calamita@uniba.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calamita
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008954:Models, Biological; D010539:Permeability / Q000187:drug effects
chemical_list: C491638:Aqp9 protein, mouse; D020346:Aquaporins; D005947:Glucose; D005990:Glycerol
keywords: Aquaglyceroporin channels; Differential equations; Glucose homeostasis; Insulin; Least-squared approximation; Membrane glycerol permeability