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Retention of acetylcarnitine in chronic kidney disease causes insulin resistance in skeletal muscle

Research Project

Project/Area Number 15K08319
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionTokyo Medical University

Principal Investigator

Kobayashi Masaki  東京医科大学, 医学部, 教授 (10195810)

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)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
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)
KeywordsCKD / インスリン依存性 / カルニチン / インスリン抵抗性
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.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (1 results)

All 2015

All Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Retention of acetylcarnitine in chronic kidney disease causes insulin resistance in skeletal muscle2015

    • Author(s)
      Yasunori Miyamoto, Teruo Miyazaki, Akira Honda, Homare Shimohata, Kouichi Hirayama, Masaki Kobayashi
    • Organizer
      Kidney Week 2015
    • Place of Presentation
      San Diego, CA. USA
    • Year and Date
      2015-11-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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