Development of exercise-enhancing therapy targeting the liver-skeletal muscle network
| Project/Area Number |
18K19560
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 糖尿病 / 肥満症 / サルコペニア / 薬剤スクリーニング / 運動効果 / 健康寿命 / セレノプロテインP / ヘパトカイン / 2型糖尿病 / 分泌タンパク質 / 化合物スクリーニング / 遺伝子発現 / インスリン抵抗性 / 運動療法 / 肝臓 / 骨格筋 |
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| Outline of Final Research Achievements |
Since we found that selenoprotein P (SeP) secreted by the liver induces resistance to exercise, we conducted a screening to identify small-molecule compounds that specifically suppress SeP expression in the liver and enhance the exercise effect. As a result, we identified about 50 small-molecule compounds that potently suppress the transcriptional activity of SeP. Among these, we selected three compounds with low toxicity. We administered these compounds to liver cell lines and mice and confirmed the inhibitory effect on SeP expression.
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| Academic Significance and Societal Importance of the Research Achievements |
高齢化を背景に糖尿病、肥満症、サルコペニアが増大しており、運動効果を高める治療が求められている。今回同定したSeP発現抑制薬はこれまでにない運動効果増強薬となるだけでなく、2型糖尿病、脂肪肝、脂質異常症といった運動療法が効果を発揮するとされる多くの疾患に対しても全く新しい治療法になる可能性がある。さらに運動療法が持つ寿命延長効果をも増強することが出来れば、健康寿命延長薬の開発につながることが期待される。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Circulating Concentrations of Insulin Resistance-Associated Hepatokines, Selenoprotein P and Leukocyte Cell-Derived Chemotaxin 2, during an Oral Glucose Tolerance Test in Humans2019
Author(s)
Mohri K, Misu H, Takayama H, Ishii KA, Kikuchi A, Lan F, Enyama Y, Takeshita Y, Saito Y, Kaneko S,Takamura T.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 3
Pages: 373-378
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-03-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Induction of Selenoprotein P mRNA during Hepatitis C Virus Infection Inhibits RIG-I-Mediated Antiviral Immunity.2019
Author(s)
Murai K, Honda M, Shirasaki T, Shimakami T, Omura H, Misu H, Kita Y, Takeshita Y, Ishii KA, Takamura T, Urabe T, Shimizu R, Okada H, Yamashita T, Sakai Y, Kaneko S.
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Journal Title
Cell Host Microbe
Volume: 10;25(4)
Issue: 4
Pages: 588-601
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Endogenous Selenoprotein P, a Liver-Derived Secretory Protein, Mediates Myocardial Ischemia/Reperfusion Injury in Mice.2018
Author(s)
Chikata A, Kato T, Usuda K, Fujita S, Maruyama M, Nagata Y, Sakagami S, Kanamori N, Yaegashi T, Saeki T, Kusayama T, Usui S, Furusho H, Kaneko S, Takamura M.
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Journal Title
Int J Mol Sci.
Volume: 19
Issue: 3
Pages: 878-878
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serum selenoprotein P, but not selenium, predicts future hyperglycemia in a general Japanese population.2018
Author(s)
Oo SM, Misu H, Saito Y, Tanaka M, Kato S, Kita Y, Takayama H, Takeshita Y, Kanamori T, Nagano T, Nakagen M, Urabe T, Matsuyama N, Kaneko S, Takamura T.
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Journal Title
Sci Rep.
Volume: 8
Issue: 1
Pages: 16727-16727
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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