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2001 Fiscal Year Final Research Report Summary

Abnormality of protein kinase C activity and gap junction activity in diabetic vascular tissues

Research Project

Project/Area Number 11671126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionKyushu University

Principal Investigator

INOGUCHI Toyoshi  Faculty of medicine, Kyushu University, Associate Prof., 医学部・附属病院, 講師 (00294926)

Project Period (FY) 1999 – 2001
KeywordsDiabetes / Vascular complication / Gap junction / Connexin / Protein kinase C / Impaired conduction
Research Abstract

Hyperglycemia appears to be an important etiologic factor in the development of micro- and macrovascular complications in diabetic patients. However, its detailed molecular mechanism remains unclear. Among various possible mechanisms, it is widely accepted that high glucose level and diabetic state induces protein kinase c (PKC) activation in vascular cells in culture and vascular tissues of diabetic animals. Gap junctions are clusters of membrane channels that permit the intercellular exchange of ions and second messengers between adjacent cells. Gap junctional intercellular communication (GJIC) plays an important role in cardiovascular tissue homeostasis. In this study, we report that GJIC in cultured vascular cells such as endothelial cells and smooth muscle cells is inhibited by high glucose level. Furthermore, we show that it is mediated by PKC-dependent excessive phosphorylation of connexin-43 that is the main functional component of gap junction in vascular cells. In addition, it is also shown that, in diabetic rats, PKC-dependent excessive phosphorylation of connexin-43 induces the impairment of ventricular conduction in heart.
In conclusion, these results suggest that PKC -dependent impairment of GJIC may lead to various disorders of cardiovascular homeostasis and contribute to cardiovascular dysfunctions associated with diabetes.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Inoguchi T et al.: "High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells"Diabetes. 49. 1939-1945 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yu H-Y et al.: "Saturated non-esterified fatty acids stimulate de novo diacyiglycerol synthesis and protein kinase c activity in cultured aortic smooth muscle cells"Diabetologia. 44. 614-620 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoguchi T et al.: "Altered gap junction activity in cardiovascular tissues of diabetes"Med Electron Microsc. 34. 86-91 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kakimoto M et al.: "Accumulation of 8-hydroxy-2'-deoxyguanosine and mitochondrial DNA in kidney of diabetic rats"Diabetes. 51. 1588-1595 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井口登興志, 他: "糖尿病における酸化ストレスの亢進とその機序-血管壁細胞NAD(P)Hオキシターゼとミトコンドリアの役割"医学のあゆみ、酸化ストレス-フリーラジカル医学生物学の最前線. 別冊. 266-269 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井口登興志, 他: "高血糖による細胞内酸化ストレス増強機序-プロテインキナーゼC活性化とNAD(P)Hオキシダーゼ"Diabetes Frontier. 13. 174-178 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoguchi T et al.: "High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells"Diabetes. 49. 1939-1945 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yu HY et al.: "Saturated non-esterified fatty acids stimulate de novo diacylglycerol synthesis and protein kinase c activity in cultured aortic smooth muscle cells"Diabetologia. 44. 614-620 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoguchi T et al.: "Altered gap junction activity in cardiovascular tissues of diabetes"Med Electron Microsc. 34. 86-91 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakimoto M: "Accumulation of 8-hydroxy-2'-deoxyguanosine and mitochondrial DNA in kidney of diabetic rats"Diabetes. 51. 1588-1595 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoguchi T et al.: "The mechanism of enhanced oxidative stress in diabetes-role of NAD(P)H oxidase and mitochondria"Progress in Medicine : Oxidative stress. 266-269 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoguchi T et al.: "The mechanism of enhanced oxidative stress induced by high glucose-role of protein kinase C activation and NAD(P)H oxidase"Diabetes Frontier. 13. 174-178 (2002)

    • 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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