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2001 Fiscal Year Final Research Report Summary

Is lipotoxicity caused by the intracellular accumulation ofacyl CoA ?

Research Project

Project/Area Number 12470229
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionThe University of Tokushima

Principal Investigator

KUWAJIMA Masamichi  The Tokushima University, School of Medicine, Associate Professor, 医学部, 助教授 (00205262)

Co-Investigator(Kenkyū-buntansha) MIZUNO Akira  The Tokushima University, Medicine School Hospital, Research Associate, 医学部・附属病院, 助手 (80219641)
NOMA Yoshihiko  The Tokushima University, Medicine School Hospital, Associate Professor, 医学部・附属病院, 講師 (10218349)
DOI Toshio  The Tokushima University, School of Medicine, Professor, 医学部, 教授 (60183498)
SHIMABUKURO Michio  University of the Ryukyus, Faculty of Medicine, Assistant professor, 医学部・附属病院, 講師 (60271144)
ISHIMURA Kazunori  The Tokushima University, School of Medicine, Professor, 医学部, 教授 (90112185)
Project Period (FY) 2000 – 2001
Keywordscarnitine / carintine transporter / insulin / JVS mouse / octn2 / glucagon / 2-DG uptake / fatty acid
Research Abstract

Long chain fatty acid is thought to be a strong cause of hyperglycemia (Lipotoxicity). This concept is accepted by most investigators. However, the intracellular mechanism remains unclear. Therefore, we analyzed as follows.
1. Juvenile visceral steatosis (JVS) mouse, which we reported in 1991, serves as an animal model of primary carnitine deficiency. Because JVS mouse has a defective carnitine transporter (octn 2) and intracellular carnitine level remains low, long chain acyl-CoA is supposed to be accumulated in pancreatic islet cells or cardiac myocytes. Therefore we analyzed the islets and heart.
(1) Size of islet of JVS mouse was small. By HE staining, content of glucagon was maintained, however content of pancreatic polypeptide was decreased. Some cells conserved the amount of insulin, but some did not.
(2) Carnitine transport activity in cultured myocyte of JVS mouse was decreased by about 20 percent of normal control at 25 μ M free carnitine level which is the physiological concentration in serum. Free carnitine level in JVS mouse heart is about 1-2 percent of normal control. In such a case, uptake rate of 2-deoxyglucose was eleven times higher than that of control.
2. To know the mechanism the fatty acid toxicity on β -cell function, insulinoma cell line INS-1 was incubated with palmitate. Palmitate caused the accumulation of triacylglycerol and expression rate (phosphorylated Akt/Akt) was increased. Also, activation of NFk β signal transduction was observed. Therefore, it is suggested that metabolic derangement by long-chain fatty acid was, in part, caused by phosphorylated Akt and activated NFk β signal transduction.
3. Diabetic heart showed a higher Ca^<2+> content and it was inhibited by T_3.

  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Y.Oshiro: "Triodothyronine concomitartly inhibits calcium overoad and postischemic myocardial stunning in diabetic rats"Life Sci.. 69・16. 1907-1918 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桑島正道: "血糖測定器の測定原理"プラクティス. 18. 502-505 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桑島正道: "原発性カルニチン欠乏症"日本臨床. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桑島正道: "続発性カルニチン欠乏症"日本臨床. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桑島正道: "血中グルコース濃度の測定原理とその誤差の要因"日本臨床. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桑島正道: "血糖自己測定(SMBG)指導ガイド"日本医学出版社(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oshiro,Y.: "Triiodothyronine concomitantly inhibits calcium overload and postischemic myocardial stunning in diabetic rats."Life Sci.. 69. 1907-1918 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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