| Project/Area Number |
16K09745
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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 | Kyoto University |
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Principal Investigator |
HARADA NORIO 京都大学, 医学研究科, 助教 (50530169)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | インクレチン / GIP / GLP-1 / 脂肪酸 / GPR40 / GPR120 / 肥満 / ＧＩＰ / 脂肪酸受容体 / K細胞 |
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| Outline of Final Research Achievements |
Free fatty acid receptors GPR120 and GPR40 are expressed in enteroendocrine K cells, and their activation induces the secretion of the incretin GIP. However, the role of these receptors in fat-induced GIP secretion in vivo and the associated mechanisms are unclear. In this study, we investigated oil-induced GIP secretion in GPR120-knockout (KO) and GPR40-KO mice.
GPR120/GPR40 double KO mice showed no GIP secretion by oil. Oil-induced GIP secretion was reduced by 50% and 80% in GPR120-KO and GPR-KO mice, respectively, compared with wild-type mice. GPR120-KO and GPR-KO mice also exhibited substantially decreased levels of CCK that promotes bile and pancreatic lipase secretion. Notably, treatment with a CCK analog resulted in recovery of oil-induced GIP secretion in GPR120-KO mice but not in GPR40-KO mice. These results indicate that GPR120 and GPR40 are essential for oil-induced gastric inhibitory polypeptide secretion, and GPR120-induced GIP secretion is indirectly mediated by CCK.
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| Academic Significance and Societal Importance of the Research Achievements |
肥満は様々な生活習慣病の中で治療が困難な問題であり、２型糖尿病や心血管疾患の危険因子となる。肥満の減少は糖尿病や動脈硬化疾患の発症や進展予防に寄与できる可能性がある。
GIPは腸内分泌Ｋ細胞から分泌されるインクレチンであり、膵臓β細胞からのインスリン分泌を増強する。またGIPは、高脂肪食餌誘発性肥満およびインスリン抵抗性を増強する。 したがって、脂肪誘発性GIP分泌のメカニズムを理解しその分泌を抑制することは、肥満症の治療戦略につながる可能性がある。
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