| Project/Area Number |
15K08319
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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 |
Pathological medical chemistry
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
本多 彰 東京医科大学, 医学部, 教授 (10468639)
宮崎 照雄 東京医科大学, 医学部, 講師 (60532687)
下畑 誉 東京医科大学, 医学部, 准教授 (90516030)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | CKD / インスリン依存性 / カルニチン / インスリン抵抗性 |
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| Outline of Final Research Achievements |
Insulin resistance (IR) occurs frequently in patients with chronic kidney disease (CKD), but the mechanisms are unclear. An increase in the mitochondrial acetyl-CoA (AcCoA) causes IR in skeletal muscles, and mitochondrial AcCoA level is regulated by carnitine acetyltransferase (CrAT) that exchanges acetyl-moiety between CoA and carnitine (CT). Present study evaluated hypothesis that retention of acetylcarnitine (AcCT) might cause IR in CKD patients. Serum AcCT concentration in CKD patients was significantly increased with reduction of renal function. AcCT treatments on cultured myotubes significantly inhibited insulin-dependent glucose uptake. The added AcCT was converted to CT via reverse CrAT reaction, and thus the AcCoA concentration and AcCoA/CoA ratio in mitochondria were significantly elevated. The results suggest that increased serum AcCT in CKD patients causes AcCoA accumulation in mitochondria, which leads to IR in skeletal muscle.
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