Identification of Epac2A agonists as novel anti-diabetic agents.
| Project/Area Number |
25860749
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Metabolomics
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| Research Institution | Kobe University |
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Principal Investigator |
Sugawara Kenji 神戸大学, 医学(系)研究科(研究院), 研究員 (70645217)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Epac2A / インスリン分泌 / 糖尿病 |
|---|
| Outline of Final Research Achievements |
We attempted to discover novel small molecules that activate Epac2A by in silico similarity search using sulfonylureas and cAMP as queries, followed by the measurement of insulin secretion. Among 170 compounds selected by in silico similarity search, we found ten compounds that stimulate insulin secretion. By Rap1-GTP assay, one compound was indicated to stimulate Rap1 which is a substrate of Epac2A. Based on the structure-activity relationship of its derivatives, we identified compound X as being the most potent insulin secretagogue.
Oral administration of compound X significantly suppressed rises in blood glucose levels after glucose load in wild-type mice and improved glucose tolerance in the Goto-Kakizaki (GK) rat, a model of type 2 diabetes with impaired insulin secretion. Our data indicate that compound X is a novel insulin secretagogue, which serves as a lead compound for development of a new anti-diabetic agent.
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Glutamate acts as a key signal linking glucose metabolism to incretin/cAMP action to amplify insulin secretion2014
Author(s)
Gheni G, Ogura M, Iwasaki M, Yokoi N, Minami K, Nakayama Y, Harada K, Hastoy B, Wu X, Takahashi H, Kimura K, Matsubara T, Hoshikawa R, Hatano N, Sugawara K, Shibasaki T, Inagaki N, Bamba T, Mizoguchi A, Fukusaki E, Rorsman P, Seino S
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Journal Title
Cell Rep
Volume: 9
Issue: 2
Pages: 661-673
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Chronic Arsenic Exposure Impairs Pancreatic Function.2016
Author(s)
Carmean CM, Kirkley AG, Yokoi N, Hoshikawa R, Honda K, Gheni G, Sugawara K, Takahashi H, Sargis RM, Seino S.
Organizer
17th International Group on Insulin Secretion Conference
Place of Presentation
Nice, France
Year and Date
2016-04-05
Related Report
Int'l Joint Research
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[Book] 糖尿病学2015
Author(s)
菅原健二、清野 進.
Total Pages
12
Publisher
西村書店
Related Report
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