| Project/Area Number |
15K09384
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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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| Research Field |
Metabolomics
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
HOSODA Kiminori 京都大学, 大学院医学研究科, 教授 (40271598)
TOMITA Tsutomu 京都大学, 大学院医学研究科, 助教 (50402897)
MASHIMO Tomoji 京都大学, 大学院医学研究科, 准教授 (80397554)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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 / インクレチン分泌 / 糖尿病 / グルコース応答性 / インスリン顆粒 / 惹起経路 / 増幅経路 |
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| Outline of Final Research Achievements |
We find here that sphingosine kinase 1-interacting protein (SKIP, also called Sphkap) is highly expressed in pancreatic b-cells but not in a-cells. Intraperitoneal glucose tolerance test showed that plasma glucose levels were decreased and insulin levels were increased in SKIP-/- mice compared to SKIP+/+ mice, but exendin-4-enhanced insulin secretion was masked. GSIS was amplified more in SKIP-/- but exendin-4-enhanced insulin secretion was masked compared to that in SKIP+/+ islets. The ATP and cAMP content were similarly increased in SKIP+/+ and SKIP-/- islets; depolarization-evoked, PKA and cAMP-mediated insulin secretion were not affected. Inhibition of PDE activity equally augmented GSIS in SKIP+/+ and SKIP-/- islets. These results indicate that SKIP modulates GSIS by a pathway distinct from that of cAMP-, PDE- and sphingosine kinase-dependent pathways.
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