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Elucidation of signaling mechanism to other organs by small intestinal Na-dependent glucose absorption mechanism

Research Project

Project/Area Number 22K19717
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionUniversity of Shizuoka

Principal Investigator

Hayashi Hisayoshi  静岡県立大学, 食品栄養科学部, 准教授 (40238118)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords生活習慣病 / 腸管バリア / タイト結合 / Na依存性グルコース吸収機構 / クローディン15 / 陽イオン選択性 / Na-依存性共輸送 / SGLT-1 / 腸管腔内恒常性 / ナトリウム / SGLT1
Outline of Research at the Start

生活習慣病の原因は、長年の偏った食生活と、ヒト遺伝子のミスマッチに依ることが大きいと推測されている。栄養素を受け入れている腸が、他臓器にどのようなシグナルを送り、さらに食行動を変化させているかは、よく知られていない。本研究では、グルコースを通常多く摂取しない草食動物に、グルコースを摂食させた際に、小腸や生体に何が起こるかを観察することを目的とする。腸のグルコース吸収の新たな役割が解明できれば、栄養学的のみならず、生物学的に新たな概念の提唱に繋がる。

Outline of Final Research Achievements

The causes of lifestyle-related diseases are hypothesized to be due to long-term unbalanced diets and mismatches in human genes. Additionally, high intake of sugar and NaCl is also considered a cause of these diseases. However, it remains unclear how the intestine supplies the large amounts of Na necessary for nutrient absorption according to dietary intake. In this study, we examined tadpoles and frogs, which undergo a dietary shift from herbivory to carnivory, as well as genetically modified mice and rats with altered intestinal Na metabolism. The results revealed that, in all species, the barrier protein claudin-15, expressed in the intercellular spaces of the small intestinal epithelial cells, plays a crucial role in intestinal Na metabolism.

Academic Significance and Societal Importance of the Research Achievements

上皮は、生体を外部環境から保護し、臓器に特有の機能を与える。上皮を通過する物質の移動には、上皮細胞を通るものと細胞間を通るものがある。腸では、単層の上皮が内腔と分離し、病原物質の流入を防ぎつつ、栄養や水分の吸収に必要な選択的透過性を保つ。このバランスが崩れると、クローン病、潰瘍性大腸炎、糖尿病などが発生する可能性がある。本研究では、腸管上皮細胞間のNa透過性にクローディン15が関与しており、健康と疾患の理解に繋がることが明らかになった。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (6 results)

All 2023 2022

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Na+-dependent intestinal glucose absorption mechanisms and its luminal Na+ homeostasis across metamorphosis from tadpoles to frogs2023

    • Author(s)
      Noriko Ishizuka ,Mina Nagahashi ,Yuina Mochida ,Wendy Hempstock , Nozomi Nagata and Hisayoshi Hayashi
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol

      Volume: 324 Issue: 5 Pages: R645-R655

    • DOI

      10.1152/ajpregu.00249.2021

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] The effect of claudin-15 deletion on cationic selectivity and transport in paracellular pathways of the cecum and large intestine2023

    • Author(s)
      W. Hempstock, N. Nagata, N. Ishizuka and H. Hayashi
    • Journal Title

      Scientific reports

      Volume: 13 Issue: 1

    • DOI

      10.1038/s41598-023-33431-5

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ラット小腸栄養素吸収機構におけるタイト結合を介したNa+リサイクリング機構の解明2023

    • Author(s)
      塚本小雪、藤本優、尾形美晴、高林秀次、林久由
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Claudin-15 is responsible for the conductance and permselectivity of the murine cecum and large intestine2023

    • Author(s)
      N. Nagata, W. Hempstock, N. Ishizuka, H. Hayashi
    • Organizer
      日本生理学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Claudin-15 is the molecule responsible for the conductance and permselectivity of the murine cecum and large intestinal epithelia2022

    • Author(s)
      W. Hempstock, N. Nagata, N. Ishizuka, H. Hayashi
    • Organizer
      Europhysiology 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Luminal Na+ concentration is preserved in claudin-15 knockout mice fed a high Na+ diet2022

    • Author(s)
      N. Nagata, W. Hempstock, N. Ishizuka, H. Hayashi
    • Organizer
      Europhysiology 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2022-07-05   Modified: 2025-01-30  

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