| Project/Area Number |
18K17016
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57010:Oral biological science-related
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| Research Institution | Kyushu University |
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Principal Investigator |
Shusuke Iwata 九州大学, 歯学研究院, 助教 (60780062)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | アドレノメデュリン / カプサイシン / SGLT1 / 味覚 / SGLT-1 / グルコーストランスポーター / 歯学 / シグナル伝達 / 内分泌 |
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| Outline of Final Research Achievements |
Chorda tympani (CT) nerve responses recordings in mice showed capsaicin (Cap) enhances responses to sugars and NaCl, but not to artificial sweeteners (AS) and others. I found Adrenomedulin (ADM), peptide released via axon reflex evoked by Cap stimulation, receptors were expressed in mice taste buds. ADM enhances CT nerve responses to sugars but not to AS and others. Enhancing effects of ADM on responses to sugars were abolished by pretreatment of ADM receptors inhibitor AM22-52. Recent study has demonstrated that sodium-dependent glucose cotransporters 1 (SGLT1) was expressed in T1R3-positive cells and mediate the T1R-independent sweet sensing pathway of sugars but not of AS. Interestingly, ADM enhances SGLT1 expression in rat intestine. SGLT1 inhibitor Phloridzin abolished enhancing effect of ADM, suggesting that ADM released by Cap inducing axon reflex enhances sweet taste responses via SGLT1, and our data may imply potential involvement of T1Rs-independent receptor systems.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果、Cap刺激により生じる軸索反射で放出されるADMにより、SGLT1を介した糖に対する甘味応答の増強を生じることが明らかになった。CapによるTRPV1活性化は、マウス小腸でのGLP-1の分泌を増加させ、肥満に伴い生じるインスリン抵抗性を改善し、上昇した血糖値を正常値に戻すことなどが報告されている。甘味受容細胞は、腸と同様にT1R系と糖輸送体の２つの受容体や、KATPチャネル、GLP-1などの下流分子を共有していることから、Capにより誘起される味覚修飾機構の分子基盤解明は、他臓器で生じるTRPV1を介したエネルギー・糖質代謝調節機序の理解に繋がると考えられる。
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