Coupling between phosphate and calcium homeostasis: a mathematical model.

Détails

ID Serval
serval:BIB_848700BBE16D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Coupling between phosphate and calcium homeostasis: a mathematical model.
Périodique
American Journal of Physiology. Renal Physiology
Auteur(s)
Granjon D., Bonny O., Edwards A.
ISSN
1522-1466 (Electronic)
ISSN-L
1931-857X
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
313
Numéro
6
Pages
F1181-F1199
Langue
anglais
Résumé
We developed a mathematical model of calcium (Ca) and phosphate (PO4) homeostasis in the rat to elucidate the hormonal mechanisms that underlie the regulation of Ca and PO4 balance. The model represents the exchanges of Ca and PO4 between the intestine, plasma, kidneys, bone, and the intracellular compartment, and the formation of Ca-PO4-fetuin-A complexes. It accounts for the regulation of these fluxes by parathyroid hormone (PTH), vitamin D3, fibroblast growth factor 23, and Ca2+-sensing receptors. Our results suggest that the Ca and PO4 homeostatic systems are robust enough to handle small perturbations in the production rate of either PTH or vitamin D3 The model predicts that large perturbations in PTH or vitamin D3 synthesis have a greater impact on the plasma concentration of Ca2+ ([Ca2+]p) than on that of PO4 ([PO4]p); due to negative feedback loops, [PO4]p does not consistently increase when the production rate of PTH or vitamin D3 is decreased. Our results also suggest that, following a large PO4 infusion, the rapidly exchangeable pool in bone acts as a fast, transient storage PO4 compartment (on the order of minutes), whereas the intracellular pool is able to store greater amounts of PO4 over several hours. Moreover, a large PO4 infusion rapidly lowers [Ca2+]p owing to the formation of CaPO4 complexes. A large Ca infusion, however, has a small impact on [PO4]p, since a significant fraction of Ca binds to albumin. This mathematical model is the first to include all major regulatory factors of Ca and PO4 homeostasis.

Mots-clé
Animals, Bone and Bones/metabolism, Calcium/blood, Calcium/metabolism, Calcium Phosphates/blood, Calcium Phosphates/metabolism, Cholecalciferol/metabolism, Feedback, Physiological, Female, Fibroblast Growth Factors/metabolism, Homeostasis, Intestines/metabolism, Kidney/metabolism, Male, Mice, Inbred C57BL, Models, Biological, Parathyroid Hormone/metabolism, Phosphates/blood, Phosphates/metabolism, Receptors, Calcium-Sensing/metabolism, alpha-2-HS-Glycoprotein/metabolism, FGF23, PTH, calcium, homeostasis, mathematical model, phosphate, vitamin D3
Pubmed
Web of science
Création de la notice
15/08/2017 12:18
Dernière modification de la notice
03/03/2018 18:55
Données d'usage