A novel role of 1,25(OH)2 vitamin D3 in the regulation of intestinal Npt2b and renal Npt2c in hypophosphatemia

Autor: Linto Thomas, Jianxiang Xue, Jessica A. Dominguez Rieg, Timo Rieg
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
Popis: 1,25(OH)2 vitamin D3 (Vit-D3) is a hormone that is formed by the coordinated actions of the skin and kidneys and is involved in the regulation of Ca2+ and phosphate (Pi) homeostasis. Of note, the regulation of these minerals is complex and involves other hormones including parathyroid hormone and fibroblast growth factor 23. Of major importance is the renal Na+/phosphate co-transporter (Npt2a) for long-term Pi homeostasis and Npt2a knockout (Npt2a-/-) mice are hypophosphatemic. However, the impact of Vit-D3 on Pi and Ca2+ in the absence of Npt2a has never been assessed. We hypothesized that exogenous application of Vit-D3 might modulate impaired Pi homeostasis by regulating their Pi transporters in the absence of Npt2a. Here we compared the effects of subcutaneous administration of Vit-D3 (300,000 IU/kg for 4 days, q.d.) or vehicle (5% Ethanol,5% Cremophore EL, and 90% water) in male wild-type (WT) and Npt2a-/- mice (n=6/genotype and treatment). Blood samples were collected before (baseline) and after Vit-D3 treatment. In WT mice, Vit-D3 or vehicle treatment did not change plasma Pi levels compared to baseline. In contrast, Vit-D3 significantly increased (~1.7-fold) plasma Pi levels in Npt2a-/- mice compared to baseline (1.5±0.09 vs. 0.9±0.04 mmol/L, P Funding to Dr. Rieg was provided by the NIDDK grant 1R01DK110621, VA Merit Review Award IBX004968A, AHA Transformational Research Award 19TPA34850116, and NIDDK Diabetic Complications Consortium grants DK076169 and DK115255. Dr. Thomas was supported by an AHA postdoctoral grant (828731). This is the full abstract presented at the American Physiology Summit 2023 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.
Databáze: OpenAIRE