| Project/Area Number |
17K09889
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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 |
Endocrinology
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| Research Institution | Kyushu University of Health and Welfare (2019-2020)
Jichi Medical University (2017-2018) |
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Principal Investigator |
KIMURA HIROAKI 九州保健福祉大学, 薬学部, 教授 (70593622)
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| Co-Investigator(Kenkyū-buntansha) |
高橋 将文 自治医科大学, 医学部, 教授 (40296108)
渡邊 幸子 自治医科大学, 医学部, 助教 (80770619)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 免疫プロテアソーム / 糖代謝 / 脂肪細胞分化 / マクロファージ / LMP7 / 炎症 / メタボリック症候群 / 脂質代謝 / 脂肪細胞 |
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| Outline of Final Research Achievements |
It is very important to improve QOL (Quality of Life), which often is influenced by metabolic disorders and aging. Despite the fact that many medications on metabolic disorders or aging have been developed, it is always preferable to develop new types of medications for such diseases.
The immunoproteasome is known as an immune modulator and involved in the pathogenesis of autoimmune diseases. We found that deficiency of LMP7 (an enzymatic subunit of the immunoproteasome) improves glucose tolerance and insulin sensitivity. Interestingly, LMP7 in non-immune cells plays an important role in glucose tolerance and insulin sensitivity. We also found thatLMP7 deficiency increases IRS-1 in adipose tissue. In addition, both inhibition and depletion of LMP7 suppressed adipogenesis in mouse preadipocyte cell line, 3T3-L1 cells. Decrease of PPAR-g and C/EBPa was involved in the suppression of adipogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題では、免疫プロテアソームの役割について研究を進めている。研究者の多くは、
血球・免疫細胞における役割に着目しており、組織細胞におけるその役割についてはほとんど解明されていない。したがって、本研究において、組織細胞における免疫プロテアソームの役割を解明することは、免疫プロテアソームの新規の役割を見出すという点において、学術的に意義があると言える。また、我が国では高齢化が進み、生活習慣病である糖尿病の患者数も多く、血糖値をコントロールする新規の糖尿病治療薬が、本研究を基に開発されれば、本研究は社会的に意義があると言える。
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