The mechanisms of GIP secretion from enteroendocrine K cells
Project/Area Number |
25293210
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Metabolomics
|
Research Institution | Kyoto University |
Principal Investigator |
INAGAKI NOBUYA 京都大学, 医学(系)研究科(研究院), 教授 (30241954)
|
Co-Investigator(Kenkyū-buntansha) |
Norio Harada 京都大学, 医学(系)研究科, 助教 (50530169)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
|
Keywords | インクレチン / GIP / K細胞 / インスリン分泌 / 肥満 / K細胞 / GPR120 / FABP5 / RFX6 |
Outline of Final Research Achievements |
GIP is an incretin secreted from enteroendocrine K cells in response to nutrient ingestion and potentiates glucose-dependent insulin secretion from pancreatic beta-cells. Fat intake strongly stimulates GIP secretion. However, mechanisms of fat-induced GIP secretion had remained unclear, mainly because of inability to isolate K cells from intestinal epithelium. We generated GIP-green fluorescent protein knock-in (GIP-GFP) mice, in which K cells are labeled by enhanced GFP. Microarray analysis of K cells isolated from GIP-GFP mice enabled us to identify genes that are highly expressed in K cells. Among the genes, we clarified that fatty acid-binding protein 5 (FABP5) and free fatty acid receptor GPR120 play critical roles in GIP secretion in response to a single administration of fat. Furthermore, we demonstrated that transcription factors Rfx6 and Pdx1 are involved in production of GIP under High-fat diet feeding by increasing GIP gene expression in K cells.
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Report
(4 results)
Research Products
(43 results)
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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 Article] Hayakawa, N., Nakamoto, Y., Kurihara, K., Yasoda, A., Kanamoto, N., Miura, M., Inagaki, N., Togashi, K.2015
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[Journal Article] Once-weekly trelagliptin versus daily alogliptin in Japanese patients with type 2 diabetes: a randomised, double-blind, phase 3, non-inferiority study.2015
Author(s)
Inagaki, N., Onouchi, H., Maezawa, H., Kuroda, S., and Kaku, K.
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Journal Title
Lancet Diabetes Endocrinol
Volume: 3
Issue: 3
Pages: 191-191
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[Journal Article] Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K-cells of upper small intestine and has a critical role in GIP secretion after fat ingestion.2015
Author(s)
Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K, Hamasaki A, Joo E, Nasteska D, Shibue K, Harada T, Hashimoto T, Asakawa Y, Hirasawa A, Inagaki N.
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[Journal Article] Efficasy and safety of luseogliflozin added to various oal antidiabetic drugs in Japanese patients with type 2 diabetes mellitus.2015
Author(s)
Seino, Y., Inagaki, N., Haneda, M., Sasaki, T., Fukatsu, A., Ubukata, M., and Samukawa, Y.
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Journal Title
J. Diabetes Investig.
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Journal of Clinical Biochemistry and Nutrition
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Issue: 2
Pages: 140-144
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NAID
ISSN
0912-0009, 1880-5086
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[Journal Article] Fatty acid binding protein 5 (FABP5) regulates diet-induced obesity (DIO) via GIP secretion from enteroendocrine K-cells in response to fat ingestion.2015
Author(s)
Shibue, K., Yamane, S., Harada, N., Hamasaki, A., Suzuki, K., Joo, E., Iwasaki, K., Nasteska, D., Harada, T., Hayashi, Y., Adachi, Y., Owada, Y., Takayanagi, R. and Inagaki, N.
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Am J Physiol Endocrinol Metab
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[Journal Article] Increased bone turnover and possible accelerated fracture healing in a murine model with an increased circulating C-type natriuretic peptide2015
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Journal Title
Endocrinology
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Issue: 7
Pages: 2518-2529
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[Journal Article] Enteral supplement enriched with glutamine, fiber, and oligosaccharide modulates incretin and glucagon-like peptide-2 secretion.2015
Author(s)
Joo E., Muraoka A., Hamasaki A., Harada N., Yamane S., Kondo Y., Suzuki K., Nasteska D., Shibue K., Harada T., Iwasaki K., Tsuji H., Shide K., Inagaki N.
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Choudhary P, Rickels MR, Senior PA, Vantyghem MC, Maffi P, Kay TW, Keymeulen B, Inagaki N, Saudek F, Lehmann R, Hering BJ.
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[Journal Article] Ayano-Takahara S, Ikeda K, Fujimoto S, Asai K, Oguri Y, Harashima S, Tsuji H, Shide K, Inagaki N.2015
Author(s)
Ayano-Takahara S, Ikeda K, Fujimoto S, Asai K, Oguri Y, Harashima S, Tsuji H, Shide K, Inagaki N.
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Journal Title
J Diabetes Investig.
Volume: 6
Issue: 6
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[Journal Article] SYR-472, a novel once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor, in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial.2014
Author(s)
Inagaki, N., Onouchi, H., Sano, H., Funao, N., Kuroda, S., Kaku, K.
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[Journal Article] Glutamate acts as a key signal linking glucose metabolism to incretin/cAMP action to amplify insulin secretion2014
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[Journal Article] Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction2013
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Journal Title
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[Journal Article] Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity.2013
Author(s)
Suzuki K, Harada N, Yamane S, Nakamura Y, Sasaki K, Nasteska D, Joo E, Shibue K, Harada T, Hamasaki A, Toyoda K, Nagashima K, Inagaki N.
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[Presentation] 脂肪摂取と肥満
Author(s)
原田範雄 稲垣暢也
Organizer
第50回日本糖尿病学会近畿地方会
Place of Presentation
京都国際会館
Related Report
Invited
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