| Project/Area Number |
16H05326
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
原田 範雄 京都大学, 医学研究科, 講師 (50530169)
林 良敬 名古屋大学, 環境医学研究所, 准教授 (80420363)
山根 俊介 京都大学, 医学研究科, 助教 (90582156)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | インクレチン分泌 / インクレチン / GIP / GLP-1 / K細胞 / L細胞 / Incretin |
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| Outline of Final Research Achievements |
We examined FABP5 localization in K-cells before and after oral fat
intake using electron microscopy and confocal microscopy.FABP5 was present both in the nucleus and in the cytoplasm of K-cells before loading. In contrast, 60 minutes after fat loading, the intranuclear localization has disappeared. The expression of Regulator of G protein signaling 4(RGS4) was found to be elevated in the K cells of FABP5-deficient mouse. We clarified that both GPR120 and GPR40 are involved in GIP secretion after fat intake. It is suggested that GPR40 expressed in K-cells directly sense LCFA, and in contrast, GPR120 expressed in I-cells indirectly regulates GIP secretion in the presence of bile via CCK secretion.We also obtained results suggesting that carbonic anhydrase 8 (Car8), which shows high expression in L-cells, negatively regulates GLP-1 secretion in response to fatty acid stimulation.
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| Academic Significance and Societal Importance of the Research Achievements |
肥満・2型糖尿病患者の数は増加の一途をたどっており、全世界的に重要な健康問題であるが、有効かつ安全性の高い治療法は未だ確立されていないのが現状である。本研究で注目しているインクレチンはその治療標的として大変有望であり、GIP制御に関わる重要な分子としてFABP5に、GLP-1分泌制御に関与するものとしてCar8に着目し、作用機構の解明に着手している。本研究の結果、薬剤によるFABP5、Car8の制御を介してインクレチン分泌制御が可能となれば、糖尿病・肥満症の新たな治療法の開発、創薬につながることが期待され研究の意義は大きい。
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