2015 Fiscal Year Final Research Report
Investigation of exercise resistance induced by hepatokine selenoprotein P
| Project/Area Number |
25461334
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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 | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | ヘパトカイン / 運動抵抗性 / セレノプロテインP |
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| Outline of Final Research Achievements |
We have previously identified selenoprotein P (SeP) as a type 2 diabetes-upregulated hepatokine that induces insulin resistance and hyperglycemia. In this study, we propose a novel pathological concept SeP-induced exercise resistance. We have found out that SeP impairs ROS-induced AMPK phosphorylation in cultured myotubes. SeP knockout mice showed increased sensitivity to exercise training. siRNA screening revealed that LRP1 functions as a SeP receptor in cultured myotubes. This study demonstrates that overproduction of SeP induces exercise resistance by suppressing ROS/AMPK through muscle receptor LRP1. Our study opens the door for inhibitors of SeP/LRP1 axis as new drugs for physical inactivity-associated diseases such as type 2 diabetes.
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| Free Research Field |
糖尿病学
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