| Project/Area Number |
25870483
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Metabolomics
Pathological medical chemistry
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | インスリン受容体切断 / インスリン抵抗性 / 可溶性インスリン受容体 |
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| Outline of Final Research Achievements |
Soluble insulin receptor (sIR), the ectodomain of insulin receptor (IR), is detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. The present study demonstrated cleavage of IR in HepG2 cells treated with high glucose, and O-linked N-acetylglucosamine modification was involved in high-glucose-induced IR cleavage. Additionally, this study showed ectodomain shedding of IR is dependent on the presence of calcium-ion, raised the possibility that calpain 2, a calcium-dependent protease, is a cleavage enzyme of IR. This model also demonstrated that IR cleavage is partially responsible for the impaired insulin signaling induced by high glucose. These findings suggests that cleavage of IR is a possible component of insulin signaling in cells, and may offer considerable insight into insulin resistance-related disease.
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