ID | 119347 |
Title Alternative | 5/6腎臓摘出ラットにおいて増加する腸管腔内無機リン酸は亜鉛吸収を抑制する
INORGANIC PHOSPHATE SUPPRESSES INTESTINAL Zn ABSORPTION
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Author |
Okumura, Yosuke
Tokushima University
Abe, Kotaro
Tokushima University
Sakai, Shoko
Tokushima University
Mori, Yuki
Tokushima University
Adachi, Yuichiro
Tokushima University
Takikawa, Masaki
Tokushima University
Kitamura, Ayano
Tokushima University
Ohnishi, Kohta
Tokushima University
Masuda, Masashi
Tokushima University
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Kambe, Taiho
Kyoto University
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Keywords | chronic kidney disease
zinc deficiency
hyperphosphatemia
dietary phosphate
zinc transporter
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Content Type |
Thesis or Dissertation
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Description | Zinc (Zn) is an essential trace element in various biological processes. Chronic kidney disease (CKD) often leads to hypozincemia, resulting in further progression of CKD. In CKD, intestinal Zn absorption, the main regulator of systemic Zn metabolism, is often impaired; however, the mechanism underlying Zn malabsorption remains unclear. Here, we evaluated intestinal Zn absorption capacity in a rat model of CKD induced by 5/6 nephrectomy (5/6 Nx). Rats were given Zn and the incremental area under the plasma Zn concentration-time curve (iAUC) was measured as well as the expression of ZIP4, an intestinal Zn transporter. We found that 5/6 Nx rats showed lower iAUC than sham-operated rats, but expression of ZIP4 protein was upregulated. We therefore focused on other Zn absorption regulators to explore the mechanism by which Zn absorption was substantially decreased. Because some phosphate compounds inhibit Zn absorption by coprecipitation and hyperphosphatemia is a common symptom in advanced CKD, we measured inorganic phosphate (Pi) levels. Pi was elevated in not only serum but also the intestinal lumen of 5/6 Nx rats. Furthermore, intestinal intraluminal Pi administration decreased the iAUC in a dose-dependent manner in normal rats. In vitro, increased Pi concentration decreased Zn solubility under physiological conditions. Furthermore, dietary Pi restriction ameliorated hypozincemia in 5/6 Nx rats. We conclude that hyperphosphatemia or excess Pi intake is a factor in Zn malabsorption and hypozincemia in CKD. Appropriate management of hyperphosphatemia will be useful for prevention and treatment of hypozincemia in patients with CKD.
NEW & NOTEWORTHY We demonstrated that elevated intestinal luminal Pi concentration can suppress intestinal Zn absorption activity without decreasing the expression of the associated Zn transporter. Increased intestinal luminal Pi led to the formation of an insoluble complex with Zn while dietary Pi restriction or administration of a Pi binder ameliorated hypozincemia in chronic kidney disease model rats. Therefore, modulation of dietary Pi by Pi restriction or a Pi binder might be useful for the treatment of hypozincemia and hyperphosphatemia. |
Journal Title |
American Journal of Physiology-Renal Physiology
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ISSN | 1931857X
15221466
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NCID | AA11118857
AA12070596
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Publisher | American Physiological Society
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Volume | 326
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Issue | 3
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Start Page | F411
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End Page | F419
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Published Date | 2024-02-21
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Remark | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Yosuke Okumuraの学位論文として提出され,学位審査・授与の対象となっている。 |
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3807号
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Diploma Number | 甲栄第306号
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Granted Date | 2024-03-22
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Degree Name |
Doctor of Nutritional Science
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Grantor |
Tokushima University
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departments |
Medical Sciences
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