| Project/Area Number |
13671202
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Nippon Medical School |
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Principal Investigator |
OIKAWA Shinichi Nippon Medical School, Professor, 医学部, 教授 (30142946)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAWA Teruo Tohoku University Graduate School of Life Science and Agriculture, Professor, 大学院・農学研究科, 教授 (20157639)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | pancreatic β-cell / oxidized stress / insulin secretion / lipid peroxide / Hit-Y15 cell / oxLDL / 糖尿病 / 酸化LDL / β細胞 |
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| Research Abstract |
It is believed that lipid peroxidation is a main mechanism in atherogenesis from the various studies on the relationships between lipid peroxides and vascular cells. However, its effect on the other cell types has not been studied. It has been suggested that insulin secretary cell of pancreas (β-cell) was weak for oxidized stress. Therefore we challenged Hit-T15 cell, which is a β-cell derived from hamster pancreatic tumor cell, to clarify the effect of phospholipid peroxides on insulin secretion. We added native phosphatidylcholine (PC), phosphatidylcholine hydroperoxide (PCOOH) and lysophosphatidylcholine (LysoPC) in the culture of HIT-T15 cell. LysoPC significantly decreased the expression of preproinsulin mRNA, intracellular insulin content, and insulin secretion. PCOOH effect did not affect on the preproinsulin mRNA expression, but decreased intracellular insulin level and insulin secretion. These oxidized phospholipids would be the components of oxidized LDL (oxLDL). Therefore we studied the effect of oxLDL in the similar experiments as Hit-T15cell culture with LysoPC as comparison with native LDL (nLDL) and acerylated LDL (AcLDL). OxLDL significantly decreased the expression of preproinsulin mRNA, intracellular insulin content, and insulin secretion as same as LysoPC. On the other hand nLDL or AcLDL had no effects. LysoPC and oxLDL did not affect MTT assay as evaluation of cell viability. These results suggested that oxLDL disturbed insulin metabolism of β-cell to decrease insulin secretion via PCOOH and PC. We proposed that oxidized stress would be diabetogenic by the effect of oxLDL.
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