Pathophysiological role of ghrelin in impaired GLP-1 secretion in tyte 2 diabetes
Project/Area Number |
15K09397
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Jichi Medical University |
Principal Investigator |
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Project Period (FY) |
2015-10-21 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | インスリン分泌 / 糖代謝 / 糖尿病 |
Outline of Final Research Achievements |
On the basis of intestinal GLP-1 action that potentiates glucose-induced insulin release, incretin-based medicines have been widely used to treat type 2 diabetic patients. Gastric hormone ghrelin, in contrast, attenuates GLP-1-potentiated insulin release and GLP-1 release. GLP-1 and ghrelin are released in a reciprocal pattern. Therefore, the increased ghrelin/GLP-1 ratio in preprandial periods effectively prevents hypoglycemia and induces appetite. In contrast, the decreased ghrelin/GLP-1 ratio in postprandial periods effectively induces satiety and promotes disposal of elevated blood glucose. The interplay of ghrelin and GLP-1 may play a role in the systemic control of feeding and glucose metabolism, providing a novel strategy to treat type 2 diabetes with impaired insulin release and obesity with hyperphagia.
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Academic Significance and Societal Importance of the Research Achievements |
血中グレリン濃度は、食前に高値を示し食後速やかに低下する。一方、GLP-1はグレリンと正反対の血中動態を示し、食後、小腸から分泌されインスリン分泌を促進する。糖尿病ではGLP-1分泌が低下しており、インスリン分泌不全の一因と考えられているが、その病態生理は未解明である。本研究で、グレリンがGLP-1分泌を抑制していることが示され、糖尿病の病因解明の新たな布石となることが期待される。グレリン阻害によるGLP-1分泌促進とGLP-1作用増強は、GLP-1関連薬の効果を増強する新たなコンセプトによるインスリン分泌促進薬の開発基盤となり得る。
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Report
(5 results)
Research Products
(17 results)
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[Journal Article] Inhibition of Y1 receptor signaling improves islet transplant outcome2017
Author(s)
Loh Kim、Shi Yan-Chuan、Walters Stacey、Bensellam Mohammed、Lee Kailun、Dezaki Katsuya、Nakata Masanori、Ip Chi Kin、Chan Jeng Yie、Gurzov Esteban N.、Thomas Helen E.、Waibel Michaela、Cantley James、Kay Thomas W.、Yada Toshihiko、Laybutt D. Ross、Grey Shane T.、Herzog Herbert
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Journal Title
Nature Communications
Volume: 8
Issue: 1
Pages: 490-490
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Endogenous α2A-adrenoceptor-operated sympathoadrenergic tones attenuate insulin secretion via cAMP/TRPM2 signaling.2017
Author(s)
Ito K, Dezaki K, Yoshida M, Yamada H, Miura R, Rita RS, Ookawara S, Tabei K, Kawakami M, Hara K, Morishita Y, Yada T, Kakei M
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Journal Title
Diabetes
Volume: 66(3)
Issue: 3
Pages: 699-709
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] The beta-cell GHSR and downstream cAMP/TRPM2 signaling account for insulinostatic and glycemic effects of ghrelin.2015
Author(s)
Kurashina T, Dezaki K, Yoshida M, Sukma Rita R, Ito K, Taguchi M, Miura R, Tominaga M, Ishibashi S, Kakei M, Yada T
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Journal Title
Sci Rep
Volume: 5
Issue: 1
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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