Role of fatty acid receptor GPR120 and GPR40 in oil-induce GIP secretion
| 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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Report
(4 results)
Research Products
(37 results)
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[Journal Article] Sphingosine kinase 1-interacting protein is a dual regulator of insulin and incretin secretion2019
Author(s)
Liu Y, Harashima SI, Wang Y, Suzuki K, Tokumoto S, Usui R, Tatsuoka H, Tanaka D, Yabe D, Harada N, Hayashi Y, Inagaki N.
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Journal Title
The FASEB Journal
Volume: 33
Pages: 0-0
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Medium-chain triglyceride diet stimulates less GIP secretion and suppresses body weight and fat mass gain compared with long-chain triglyceride diet.2019
Author(s)
Murata Y, Harada N, Yamane S, Iwasaki K, Ikeguchi E, Kanemaru Y, Harada T, Sankoda A, Shimazu-Kuwahara S, Joo E, Poudyal H, Inagaki N.
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Journal Title
Am J Physiol Endocrinol Metab.
Volume: -
Related Report
Peer Reviewed
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[Journal Article] Transcriptional factor Pdx1 is involved in age-related GIP hypersecretion in mice.2018
Author(s)
Ikeguchi E, Harada N, Kanemaru Y, Sankoda A, Yamane S, Iwasaki K, Imajo M, Murata Y, Suzuki K, Joo E, Inagaki N.
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Journal Title
American Journal of Physiology-Gastrointestinal and Liver Physiology
Volume: 315
Pages: 272-272
DOI
Related Report
Peer Reviewed
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[Journal Article] Glucose-dependent insulinotropic polypeptide is required for moderate high fat diet, but not high carbohydrate diet-induced weight gain.2018
Author(s)
Maekawa R, Ogata H, Murase M, Harada N, Suzuki K, Joo E, Sankoda A, Iida A, Izumoto T, Tsunekawa S, Hamada Y, Oiso Y, Inagaki N, Arima H, Hayashi Y, Seino Y.
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Journal Title
American Journal of Physiology-Endocrinology and Metabolism
Volume: 6
Pages: 111-112
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Whole-exome sequencing in a Japanese family with highly aggregated diabetes identifies a candidate susceptibility mutation in ADAMTSL3.2018
Author(s)
Jambaljav B, Tanaka D, Nagashima K, Harashima SI, Harada N, Harada T, Fujiwara Y, Wang Y, Liu Y, Tabara Y, Matsuda F, Koizumi A, Inagaki N.
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Journal Title
Diabetes Res Clin Pract
Volume: 135
Pages: 143-149
Related Report
Peer Reviewed
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[Journal Article] Inhibition of Gastric Inhibitory Polypeptide Receptor Signaling in Adipose Tissue Reduces Insulin Resistance and Hepatic Steatosis in High-Fat Diet-Fed Mice.2017
Author(s)
Joo E, Harada N, Yamane S, Fukushima T, Taura D, Iwasaki K, Sankoda A, Shibue K, Harada T, Suzuki K, Hamasaki A, Inagaki N.
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Journal Title
Diabetes
Volume: 66
Pages: 868-868
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Long chain free fatty acid receptor GPR120 mediates oil-induced GIP secretion through CCK in male mice.2017
Author(s)
19.Sankoda A, Harada N, Iwasaki K, Yamane S, Murata Y, Shibue K, Thewjitcharoen Y, Suzuki K, Harada T, Kanemaru Y, Shimazu-Kuwahara S, Hirasawa A, Inagaki N.
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Journal Title
Endocrinology
Volume: In press
Pages: 0-0
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Plasma incretin levels and dipeptidyl peptidase-4 activity in patients with obstructive sleep apnea.2016
Author(s)
Matsumoto T, Harada N, Azuma M, Chihara Y, Murase K, Tachikawa R, Minami T, Hamada S, Tanizawa K, Inouchi M, Oga T, Mishima M, Chin K.
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Journal Title
Annals of the American Thoracic Society.
Volume: 13
Pages: 1378-1378
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Sitagliptin monotherapy has better effect on insulinogenic index than glimepiride monotherapy in Japanese patients with type 2 diabetes mellitus: a 52-week, multicenter, parallel-group randomized controlled trial.2016
Author(s)
Kondo Y, Harada N, Hamasaki A, Kaneko S, Yasuda K, Ogawa E, Harashima S, Yoneda H, Fujita Y, Kitano N, Nakamura Y, Matsuo F, Shinji M, Hinotsu S, Nakayama T, Inagaki N.
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Journal Title
Diabetol Metab Syndr.
Volume: 27
Pages: 13098-13098
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Nardilysin is required for maintaining pancreatic β-Cell Function.2016
Author(s)
Nishi K, Sato Y, Ohno M, Hiraoka Y, Saijo S, Sakamoto J, Chen P-M, Morita Y, Matsuda S, Iwasaki K, Sugizaki K, Harada N, Mukumoto Y, Kiyonari H, Furuyama K, Kawaguchi Y, Uemoto S, Kita T, Inagaki N, Kimura T and Nishi E
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Journal Title
Diabetes.
Volume: 65
Pages: 3015-27
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] 長鎖脂肪酸受容体GPR120とGPR40は異なる機序で脂肪摂取時のGIP分泌に関与する.2018
Author(s)
三小田 亜希子, 原田 範雄, 岩﨑 可南子, 山根 俊介, 村田 由貴, 金丸 良徳, 鈴木 和代, 渋江 公尊, 原田 貴成, 城尾 恵里奈, 平澤 明, 稲垣 暢也.
Organizer
第60回日本糖尿病学会年次学術集会
Related Report
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[Presentation] 転写因子Pancreatic duodenal homeobox-1(Pdx1)は加齢に伴うGIP分泌亢進に関与する.2018
Author(s)
池口 絵理, 原田 範雄, 金丸 良徳, 三小田 亜希子, 山根 俊介, 岩﨑 可南子, 今城 正道, 村田 由貴, 鈴木 和代, 城尾 恵里奈, 稲垣 暢也.
Organizer
第31回日本糖尿病・肥満動物学会学術集会
Related Report
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[Presentation] 過食肥満下におけるインクレチンGIPの生体内への影響について.2017
Author(s)
桑原 智子, 原田 範雄, 金丸 良徳, 山根 俊介, 村田 由貴, 三小田 亜希子, 岩崎 可南子, 城尾 恵里奈, 渋江 公尊, 原田 貴成, 池口 絵理, 藤原 雄太, 稲垣 暢也.
Organizer
第60回日本糖尿病学会年次学術集会
Related Report
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