| Project/Area Number |
18K08524
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Iryo Sosei University (2020-2023)
Jichi Medical University (2018-2019) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | インスリン分泌 / 糖代謝 / 糖尿病 / オキシトシン / TRPM2 / インスリン / グルカゴン / カチオンチャネル / 視床下部 |
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| Outline of Final Research Achievements |
The neurohypophysial hormone, oxytocin (Oxt), reportedly stimulates insulin release from pancreatic islets, however, direct action of Oxt on islet insulin-releasing b-cells remains to be determined. In mouse isolated islets, Oxt increased 8.3 mM glucose-induced insulin release without altering basal insulin release at 2.8 mM glucose. Oxt potentiated glucose (8.3 mM)-induced [Ca2+]i increases in b-cells. In the presence of Oxt receptor antagonist, Oxt failed to potentiate [Ca2+]i in b-cells, indicating interaction of Oxt with its receptor. The b-cell [Ca2+]i response to Oxt was attenuated by Gq-protein inhibitor and TRP channel blocker. These results demonstrate that Oxt directly interacts with b-cells, enhancing glucose-induced [Ca2+]i increase and insulin release. Oxt may glucose-dependently activates Gq-mediated non-selective cation channels to promote Ca2+ influx through L-type Ca2+ channels, providing a potential molecular target to treat type 2 diabetes.
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| Academic Significance and Societal Importance of the Research Achievements |
血糖変動幅を小さくし血糖恒常性を高める事は糖尿病学・生理学の理想であり、内因性オキシトシンがこれを担うという申請者の発見は画期的であり、糖代謝機構の解明に貢献する学術的意義がある。オキシトシンの血糖依存的なインスリン分泌促進作用は、既存の糖尿病治療薬には無い全く新しい作用様式であり、新たな糖尿病治療薬の開発基盤を提供する。オキシトシン併用投与により、糖尿病治療薬の使用濃度を低下させることが可能となり、低血糖等の副作用頻度を軽減し糖尿病治療の安全性を高めることが期待される。
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