ヒ素による糖代謝異常における膵α細胞の役割に関する研究
Project/Area Number |
16F16418
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Research Category |
Grant-in-Aid for JSPS Fellows
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Allocation Type | Single-year Grants |
Section | 外国 |
Research Field |
Metabolomics
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Research Institution | Kobe University |
Principal Investigator |
清野 進 神戸大学, 医学研究科, 特命教授 (80236067)
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Co-Investigator(Kenkyū-buntansha) |
CARMEAN CHRISTOPHER 神戸大学, 医学研究科, 外国人特別研究員
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Project Period (FY) |
2016-10-07 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2018: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2017: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2016: ¥600,000 (Direct Cost: ¥600,000)
|
Keywords | arcenic / diabetes / insulin secretion / serotonin / glucuronidation / toxicology / Insulin Secretion / Diabetes / Endocrin Disruptors / Arsenic / Serotonin / Metabolomics / Gene Expression / Detoxification / ヒ素 / 糖尿病 / 毒物学 / インスリン / グルコース |
Outline of Annual Research Achievements |
Previously our RNA sequencing and metabolomics data identified the serotonin disposal pathway as a possible mediator of arsenic’s effects. We followed up on these results by measuring the gene expression of other serotonin metabolism-associated genes, and we measured the enzymatic rate of serotonin conjugation to glucuronic acid to form serotonin-glucuronide. Additionally, we developed a series of gene candidate knockouts. We evaluated their functional characteristics, including glucose-induced insulin secretion, serotonin levels, and serotonin glucuronidation enzymatic activity. We also confirmed that the same gene expression patterns observed in MIN6-K8 cells were also replicated in primary human islets. Both mouse and human islets up-regulated Ugt1a6a (mouse) or UGT1A6 (human) in response to arsenic exposure. A paper on these findings was published in a peer-reviewed journal.
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Research Progress Status |
平成30年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
平成30年度が最終年度であるため、記入しない。
|
Report
(3 results)
Research Products
(13 results)
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[Journal Article] Arsenic modifies serotonin metabolism through glucuronidation in pancreatic beta-cells2019
Author(s)
Carmean CM, Yokoi N, Takahashi H, Oduori OS, Kang C, Kanagawa A, Kirkley AG, Han G, Landeche M, Hidaka S, Katoh M, Sargis RM, Seino S
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Journal Title
American Journal of Physiology Endocrinology and Metabolism
Volume: 316
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Arsenic exposure induces glucose intolerance and alters global energy metabolism2018
Author(s)
Kirkley Andrew G.、Carmean Christopher M.、Ruiz Daniel、Ye Honggang、Regnier Shane M.、Poudel Ananta、Hara Manami、Kamau Wakanene、Johnson Daniel N.、Roberts Austin A.、Parsons Patrick J.、Seino Susumu、Sargis Robert M.
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Journal Title
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Volume: 314
Issue: 2
Pages: R294-R303
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Arsenic Exposure Induces Glucose Intolerance and Alterations in Global Energy Metabolism2017
Author(s)
Kirkley AG, Carmean CM, Ruiz D, Ye H, Kamau W, Regnier SM, Poudel A, Hara M, Sargis RM.
Organizer
The Endocrine Society’s 99th Annual Meeting and Expo(ENDO 2017)
Place of Presentation
Orange County Convention Center, Orlando, Forida, USA
Related Report
Int'l Joint Research
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