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MOLECULAR MECHANISM OF MESANGIAL DYSFUNCTION IN DIABETES

Research Project

Project/Area Number 04671471
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionSHIGA UNIVERSITY OF MEDICAL SCIENCE

Principal Investigator

HANEDA Masakazu  SHIGA UNIVERSITY OF MEDICAL SCIENCE, THIRD DEPARTMENT OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (60164894)

Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsDiabetic nephropathy / Mesangial cells / Glomerular hyperfiltration / Angiotensin II / Atrial natriuretic peptide / Protein kinase C / Inositol 1, 4, 5-trisphosphate / 心房性ナトリウム利尿ペプチド / 心房性ナトリウム料尿ペプチド / グアニル酸シクラーゼ
Research Abstract

Increase in glomerular filtration rates, glomerular hyperfiltration, is one of the major abnormalities in diabetic kidneys and is considered to be related to future development of diabetic nephropathy. We have previously shown that the contractile responsiveness of diabetic glomeruli to angiotensin II is reduced indicating the importance of mesangial cell dysfunction in diabetic glomerular hyperfiltration. The present study was performed to clarify the mechanism of this mesangial cell dysfunction. The following results were obtained ;
1. In mesangial cells cultured under high glucose conditions, ANP-induced cGMP accumulation was enhanced.
2. In contrast, inhibitory effects of angiotensin II on ANP-induced cGMP accumulation was reduced and the response of cellular IP3 to angiotensin II was also reduced.
3. Protein kinase C (PKC) was activated in cells cultured under high glucose conditions and the translocation of PKC alpha and zeta was observed.
4. Inhibition of PKC activities resulted in an amelioration of the reduction of angiotensin II action in cells cultured under high glucose conditions.
These results indicate that, in mesangial cells cultured under high glucose conditions, and elevation of PKC activities may desensitize the action of angiotensin II and thus result in decreased contractile responsiveness of mesangial cells to angiotensin II.Therefore, mesangial cells in diabetic state may have a tendency to relax and this mesangial cell dysfunction, contributes to the development of glomerular hyperfiltration in diabetes.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] 宇津 貫、他: "高糖濃度条件下培養メサンギウム細胞におけるプロテインキナーゼCの変化" 糖尿病. 36. 343-348 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Haneda M,et al.: "Alteration of mesangial response to ANP and angiotensin II by glucose." Kidney International. 44. 518-526 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Haneda M,et al.: "The interaction between atrial natriuretic peptide and angiotensin II in cultured glomerular mesangial cells and its disturbance in diabetes." Experimental Nephrology. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Masakazu Haneda, et al.: "Alteration of mesangial response to ANP and angiotensin II by glucose." Kidney Int. 44. 518-526 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Masakazu Haneda, et al.: "The interaction between atrial natriuretic peptide and angiotensin II in cultured glomerular mesangial cells and its disturbance in diabetes." Exp Nephrol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takashi Uzu, et al.: "Glucose enhances protein kinase C activity and induces translocation of PKC-alpha in cultured mesangial cells." J Japan Diab Soc. 36. 343-348 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 宇津 貴、他: "高糖濃度条件下培養メサンギウム細胞におけるプロテインキナーゼCの変化" 糖尿病. 36. 343-348 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Haneda M,et al.: "Alteration of mesangial response to ANP and angiotensinII by glucose." Kidney International. 44. 518-526 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Haneda M,et al.: "The interaction between atrial natriuretic peptide and angiotensinII in cultured glomerular mesangial cells and its disturbance in diabetes." Experimental Nephrology. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] 宇津 貴 他: "高糖濃度条件下培養メサンギウム細胞におけるプロテインキナーゼCの変化" 糖尿病. 36. (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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