Mathematical Modeling of Magnesium Homeostasis in Male Rats
Notice bibliographique
Résumé
Magnesium (Mg 2+ ) is an important cofactor for numerous biological processes, including protein synthesis, nucleic acid stability, and neuromuscular excitability. Extracellular magnesium is tightly regulated, with plasma [Mg 2+ ] maintained relatively constant between 1.6 and 2.3 mg/dL under normal physiological conditions. Almost all of the body’s Mg 2+ (approximately 99%) is either stored in bone or within cells (DOI: 10.1053/j.ackd.2018.01.003). A normal daily Mg 2+ intake averages around 300 mg, about half of which is absorbed by the intestine. The kidneys reabsorb 95-98% of the filtered Mg 2+ and excrete only 2-5% through urine. To understand the interplay between intestine, kidneys, and bones to maintain Mg 2+ homeostasis, we developed a computational model of Mg 2+ homeostasis for male rats and incorporated it with a male rat calcium (Ca 2+ ) homeostasis model. Our model consists of five compartments: plasma, intestine, kidneys, bones, and parathyroid gland. The model also includes parathyroid hormone and vitamin D 3 since they significantly regulate Mg 2+ and Ca 2+ homeostasis. We used this model to simulate three conditions: change in dietary Mg 2+ , change in dietary vitamin D 3 , and administration of proton-pump inhibitors. In the case of variation in dietary Mg 2+ , our model predicted that the body compensates mainly through decreasing (in case of low dietary Mg 2+ ) and increasing (in case of high dietary Mg 2+ ) urinary Mg 2+ excretion and the Mg 2+ content in the rapidly exchangeable bone pool. Change in dietary Mg 2+ does not have any significant effect on Ca 2+ homeostasis. On the other hand, change in dietary vitamin D 3 has significant effect on both Mg 2+ and Ca 2+ homeostasis, with the effect being more pronounced for Ca 2+ compared to Mg 2+ . Our model predicted significant changes in intestinal Mg 2+ and Ca 2+ absorption, PTH secretion, urinary Mg 2+ and Ca 2+ excretion, and Mg 2+ and Ca 2+ content in the rapidly exchangeable bone pool following change in dietary vitamin D 3 . Administration of proton pump inhibitors (PPIs) such as omeprazole, which are a class of medicine commonly used to reduce stomach acid production, affect Mg 2+ and Ca 2+ transport in the intestine. PPIs reduce intestinal Mg 2+ and Ca 2+ absorption by 3.5-fold and 40%, respectively. The body compensates for this huge drop in intestinal Mg 2+ absorption by tapping into the Mg 2+ stored in the rapidly exchangeable bone pool in addition to decreasing urinary Mg 2+ excretion. By contrast, the body can compensate for the drop in intestinal Ca 2+ absorption by only decreasing urinary Ca 2+ excretion. Thus, this model can be used to understand the compensatory mechanisms adopted by the body to maintain Mg 2+ and Ca 2+ homeostasis under various pathophysiological conditions and drug administrations. This work was supported by the Canada 150 Research Chair program, National Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant, and Canada Institutes of Health Research (CIHR) Project Grant to Anita Layton. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».