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Induction of cellualar dysfunction by 3-deoxyglucosome as a mechanism of uremic and diabetic complications

Research Project

Project/Area Number 11470216
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionNAGOYA UNIVERSITY

Principal Investigator

NIWA Toshimitsu  SCHOOL OF MEDICINE, NAGOYA UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (20208268)

Co-Investigator(Kenkyū-buntansha) 宮崎 高志  名古屋大学, 医学部, 医員
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥11,300,000 (Direct Cost: ¥11,300,000)
Keywords3-deoxyglucosone / diabetes mellitus / uremia / peritoneal dialysis / グルタチオンペルオキシダーゼ / 酸化ストレス
Research Abstract

To determine if 3-deoxyglucosone (3-DG) is involved in the formation of intracellular AGEs, we measured the erythrocyte levels of 3-DG and AGEs such as imidazolone and N^ε-carboxymethyllysine (CML) in hemodialysis (HD) patients with diabetes. Further, to determine if the polyol pathway is involved in the formation of erythrocyte 3-DG and AGEs, an aldose reductase inhibitor (ARI) was administered to these patients. The erythrocyte levels of 3-DG and AGEs are elevated in diabetic HD patients. The administration of ARI reduces the erythrocyte levels of 3-DG and AGEs, especially imidazolone, as well as sorbitol. Thus, 3-DG and AGEs, especially imidazolone, in the erythrocytes are produced mainly via the polyol pathway. ART may prevent diabetic and uremic complications associated with AGEs
We investigated the contribution of high glucose concentration versus the presence of glucose degradation products (GDP) on AGE formation in the peritoneal cavity. Furthermore, the activity of a single chamber bag continuous ambulatory peritoneal dialysis (CAPD) fluid to generate AGE was compared to two double chamber bag PD fluids. During the incubation of HSA with PD-fluids under conditions similar to those of CAPD, only a minor part of AGE formation, measured as CML, imidazolones and fluorescence, derives from high glucose concentration, whereas glucose degradation products, which are formed during heat sterilization are by far the more important glycation precursor. The use of double chamber bags reduces therefore AGE formation considerably. Thus, it can be suggested that also in vivo, double chamber bags can decrease AGE formation in the peritoneal cavity during CAPD.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Tsukushi S: "Increased erythrocyte 3-DG and AGEs in diabetic hemodialysis patients : Role of the polyol pathway."Kidney Int. 55. 1970-1976 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niwa T: "3-Deoxyglucosone : Metabolism, analysis, biological activity and clinical implication."J Chromatogr. 731. 23-36 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsukushi S: "Gas chromatographic/mass spectrometric analysis of erythrocyte 3-deoxyglucosone in hemodialysis patients."J Chromatogr. 731. 37-44 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takayama F: "Dialysis-related amyloidosis of the heart in long-term hemodialysis patients."Kidney Int. 59(Suppl78). S172-S176 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niwa T: "3-Deoxyglucosone and AGEs in uremic complications : nactivation of glutathione peroxidase by 3-deoxyglucosone."Kidney Int. 59(Suppl78). S37-S41 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tauer A: "In vitro formation of N^ε-(carboxymethyl) lysine and imidazolones under conditions similar to continuous ambulatory peritoneal dialysis (CAPD)."Biochem Biophys Res Commun. 280. 1408-1414 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsukushi S: "Increased erythrocyte 3-DG and AGEs in diabetic hemodialysis patients : Role of the polyol pathway."Kidney Int. 55. 1970-1976 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niwa T: "3-Deoxyglucosone : Metabolism, analysis, biological activity and clinical implication."J Chromatogr. 731. 23-36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsukushi S: "Gas chromatographic/mass spectrometric analysis of erythrocyte 3-deoxyglucosone in hemodialysis patients."J Chromatogr. 731. 37-44 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takayama F: "Dialysis-related amyloidosis of the heart in long-term hemodialysis patients."Kidney Int. 59 (Suppl 78). S172-S176 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niwa T: "3-Deoxyglucosone and AGEs in uremic complications : nactivation of glutathione peroxidase by 3-deoxyglucosone."Kidney Int. 59 (Suppl 78). S37-S41 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tauer A: "In vitro formation of N^ε-(carboxymethyl) lysine and imidazolones under conditions similar to continuous ambulatory peritoneal dialysis (CAPD)."Biochem Biophys Res Commun. 280. 1408-1414 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Brancaccio D: "Ultrastructural localization of advanced glycation end products and beta-2-microglobulin in dialysisamyloidosis."J Nephrol. 13. 129-126 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Frnake S: "Immunochemical detection of imidazolone in uremia and rheumatoid arthritis."Clin Chim Acta. 300. 29-41 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nokura K: "Dialysis-related spinal canal stenosis : A clinicopathological study on amyloid deposition and its AGE modification."J Neurol Sci. 178. 114-123 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takayama F: "Dialysis-related amyloidosis of the beart in long-term hemodialysis patients."Kidney Int. 59(Suppl78). S172-S176 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Niwa T: "3-Deoxyglucosone and AGEs in uremic complications : nactivation of glutathione peroxidase by 3-deoxyglucosone."Kidney Int. 59(Suppl78). S37-S41 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tauer A: "In vitro formation of N^e-(carboxymethyl)lysine and imidazolones under conditions similar to continuous ambulatory peritoneal dialysis (CAPD)."Biochem Biophys Res Commun. 280. 1408-1414 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsukushi, S.: "Increased erythrocyte 3-DG and AGEs in diabetic hemodialysis patients: Role of the polyol pathway."Kidney Int. 55. 1970-1976 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hammes, H-P: "Differential accumulation of advanced glycation end products in the course of diabetic retinopathy."Diabetologia. 42. 728-736 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Niwa, T.: "3-Deoxyglucosone: Metabolism, analysis, biological activity and clinical implication."J Chromatogr. 731. 23-36 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsukushi, S.: "Gas chromatographic/mass spectrometric analysis of erythrocyte 3-deoxyglucosone in hemodialysis patients."J Chromatogr. 731. 37-44 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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