Exploration of the possible role of GPR40-incretin signals in improvement of fatty liver, glucose intolerance and dyslipidemia
| Project/Area Number |
16K09780
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Tomita Tsutomu 国立研究開発法人国立循環器病研究センター, 病院, 室長 (50402897)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | GPR40 / 脂肪酸受容体 / 脂質異常症 / 糖代謝異常 / 創薬標的 / 糖尿病 / 脂肪酸 / G蛋白共役型受容体 / 創薬 / 内科 |
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| Outline of Final Research Achievements |
Though GRP40 is implicated in glucose-stimulated insulin secretion (GSIS) in vitro, GPR40 knockout (KO) mice have essentially normal glucose tolerance and insulin secretion in vivo. The aim of this study was to explore physiological significance of GPR40.In Sprague-Dawley rats, a widely used animal model in physiology and pharmacology, we applied zinc-finger nucleases and established GPR40 KO rats. Glucose and lipid metabolism were assessed in GPR40KO rats and compared with wildtype (WT) littermates.There was no significant difference between GPR40KO and WT rats in body weight and food intake. During intraperitoneal glucose tolerance test (ipGTT), glucose levels were increased in GPR40KO rats and associated with decreased insulin levels at 15min after glucose load.These results suggest phyciological implication of GPR40 in glucose metabolism.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、不明な点の多かったGPR40の役割の一端を解明した。本研究によりGPR40の治療的意義が解明する事により治療法として、GPR40作動系の薬剤開発の進展につながる。Ｇ蛋白共役型受容体によるインスリン分泌増強であれば、単剤では低血糖を来しにくいと予測される。こうした薬剤は患者の負担感が少なく、薬剤アドヒアランスが高いことが知られている。これらの取り組みにより糖脂質代謝異常の改善に寄与することが予想され、薬剤アドヒアランスを含めた患者QOLが向上することが想定され、また国民のライフスタイルなど幅広い意味で社会に与えるインパクトや貢献が期待される。
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Report
(5 results)
Research Products
(14 results)
