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ID 111600
Title Alternative
ナトリウム依存性リン酸トランスポーターとニコチンアミドホスホリボシルトランスフェラーゼは血漿無機リン酸濃度の日内変動に関与する
Liver-kidney axis and plasma Pi rhythm
Author
Miyagawa, Atsumi Tokushima University
Takahama, Wako Tokushima University
Fujii, Osamu Tokushima University
Nagamoto, Kenta Tokushima University
Kinoshita, Emi Tokushima University
Nomura, Kengo Tokushima University
Ikuta, Kayo Tokushima University
Fujii, Toru Tokushima University
Hanazaki, Ai Tokushima University
Keywords
daily oscillation
phosphate
NAD
Nampt
Npt2a
Npt2c
Content Type
Thesis or Dissertation
Description
Circulating inorganic phosphate exhibits a remarkable daily oscillation based on food intake. In humans and rodents, the daily oscillation in response to food intake may be coordinated to control the intestinal absorption, renal excretion, cellular shifts, and extracellular concentration of inorganic phosphate. However, mechanisms regulating the resulting oscillation are unknown. Here we investigated the roles of the sodium phosphate cotransporter SLC34 (Npt2) family and nicotinamide phosphoribosyltransferase (Nampt) in the daily oscillation of plasma inorganic phosphate levels. First, it is roughly linked to urinary inorganic phosphate excretion. Second, expression of renal Npt2a and Npt2c, and intestinal Npt2b proteins also exhibit a dynamic daily oscillation. Analyses of Npt2a, Npt2b, and Npt2c knockout mice revealed the importance of renal inorganic phosphate reabsorption and cellular inorganic phosphate shifts in the daily oscillation. Third, experiments in which nicotinamide and a specific Nampt inhibitor (FK866) were administered in the active and rest phases revealed that the Nampt/NAD+ system is involved in renal inorganic phosphate excretion. Additionally, for cellular shifts, liver-specific Nampt deletion disturbed the daily oscillation of plasma phosphate during the rest but not the active phase. In systemic Nampt+/- mice, NAD levels were significantly reduced in the liver, kidney, and intestine, and the daily oscillation (active and rest phases) of the plasma phosphate concentration was attenuated. Thus, the Nampt/ NAD+ system for Npt2 regulation and cellular shifts to tissues such as the liver play an important role in generating daily oscillation of plasma inorganic phosphate levels.
Journal Title
Kidney International
ISSN
00852538
15231755
NCID
AA00710996
AA11629608
Publisher
Elsevier|International Society of Nephrology
Volume
93
Issue
5
Start Page
1073
End Page
1085
Published Date
2018-02-15
Remark
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Atsumi Miyagawa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。
著者の申請により要約(2018-05-17公開)に替えて論文全文を公開(2018-08-06)
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3138号
Diploma Number
甲栄第247号
Granted Date
2018-02-22
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences