Journal of Diabetes and Its Complications
Volume 18, Issue 6 , Pages 336-342 , November 2004

Erythrocytic sorbitol contents in diabetic patients correlate with blood aldose reductase protein contents and plasma glucose levels, and are normalized by the potent aldose reductase inhibitor fidarestat (SNK-860)

  • Tomoichiro Asano

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +81-3-3815-5411 x33133; fax: +81-3-5803-1874
    • Department of Physiological Chemistry and Metabolism, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Yasushi Saito

      Affiliations

    • Second Department of Internal Medicine, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-0856, Japan
    • ,
  • Masanobu Kawakami

      Affiliations

    • Department of General Medicine, Omiya Medical Center, Jichi Medical School, 1-847 Amanuma, Omiya-ku, Saitama 330-8503, Japan
    • ,
  • Nobuhiro Yamada

      Affiliations

    • Institute of Clinical Medicine, University of Tsukuba, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576, Japan
    • ,
  • Hisakuni Sekino

      Affiliations

    • Sekino Clinical Pharmacology Clinic, 28-3, Ikebukuro 3 chome, Toshima-ku, Tokyo 171-0014, Japan
    • ,
  • Setsuo Hasegawa

      Affiliations

    • Sekino Clinical Pharmacology Clinic, 28-3, Ikebukuro 3 chome, Toshima-ku, Tokyo 171-0014, Japan
    • ,
  • Fidarestat Clinical Pharmacology Study Group

Received 5 May 2003 ,Revised 17 March 2004 ,Accepted 6 April 2004.

References 

  1. Asano T, Saito Y, Kawakami M, Yamada N  Fidarestat Clinical Pharmacology Study Group . Fidarestat (SNK-860), a potent aldose reductase inhibitor, normalizes the elevated sorbitol accumulation in erythrocytes of diabetic patients. Journal of Diabetes and Its Complications. 2002;16:133–138
  2. Gabbay KH. Hyperglycemia, polyol metabolism, and complications of diabetes mellitus. Annual Review of Medicine. 1975;26:521–536
  3. Gabbay KH, Merola LO, Field RA. Sorbitol pathway: presence in nerve and cord with substrate accumulation in diabetes. Science. 1966;151:209–210
  4. Hamada Y, Kitoh R, Raskin P. Crucial role of aldose reductase activity and plasma glucose level in sorbitol accumulation in erythrocytes from diabetic patients. Diabetes. 1991;40:1233–1240
  5. Ho ECM, Lam KSL, Chung SSM, Chung SK. Aldose reductase-deficient mice are alleviated from the depletion of GSH in the peripheral nerve and MNCV deficit associated with diabetes. Diabetes. 2001;50(Suppl. 2):A59
  6. Hotta N, Toyoda T, Matsuoka K, Shigeta Y, Kikkawa R, Kaneko T, et al. Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: 52-week multicenter placebo-controlled double-blind parallel group study. Diabetes Care. 2001;24:1776–1782
  7. Kamon N, Mabuchi H, Takeda R, Terashima H. Effects of aldose reductase inhibitor (ONO-2235) on human erythrocyte sorbitol concentrations in 75 g oral glucose tolerance tests. Hormone and Metabolic Research. 1991;23:226–229
  8. Kracke GR, Preston GG, Stanley TH. Identification of a sorbitol permease in human erythrocytes. American Journal of Physiology. 1994;266(2 Pt 1):C343–C350
  9. Malone JI, Knox G, Benford S, Tedesco TA. Red cell sorbitol. An indicator of diabetic control. Diabetes. 1980;29:861–864
  10. Malone JI, Leavengood H, Peterson MJ, O'Brien MM, Page MG, Aldinger CE. Red blood cell sorbitol as an indicator of polyol pathway activity. Inhibition by sorbinil in insulin-dependent diabetic subjects. Diabetes. 1984;33:45–49
  11. Mizuno K, Kato N, Makino M, Suzuki T, Shindo M. Continuous inhibition of excessive polyol pathway flux in peripheral nerves by aldose reductase inhibitor fidarestat leads to improvement of diabetic neuropathy. Journal of Diabetes and Its Complications. 1999;13:141–150
  12. Nishimura C, Hamada Y, Tachikawa I, Gui T, Tsubouchi T, Hotta N, et al. Enzyme immunoassay for aldose reductase. Clinical Chemistry. 1994;40:889–894
  13. Oates PJ. Polyol pathway and diabetic peripheral neuropathy. International Review of Neurobiology. 2002;50:325–392
  14. Pfeifer MA, Schumer MP. Clinical trials of diabetic neuropathy: past, present, and future. Diabetes. 1995;44:1355–1361
  15. Raskin P, Rosenstock J. Aldose reductase inhibitors and diabetic complications. American Journal of Medicine. 1987;83:298–306
  16. Shigeta H, Nakano K, Nakai M, Mori H, Shigeta M, Takagi S, et al. The effect of ONO-2235 on the sorbitol content of erythrocytes in patients with diabetic neuropathy. In:  Sakamoto N,  Kinoshita JH,  Kador PF,  Hotta N editor. Polyol pathway and its role in diabetic complications. Amsterdam: Elsevier Science Publisher BV; 1988;p. 553–558
  17. Sima AAF, Bril V, Nathaniel V, McEwen TAJ, Brown MB, Lattimer SA, et al. Regeneration and repair of myelinated fibers in sural-nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil. New England Journal of Medicine. 1988;319:548–555
  18. Sobajima H, Aoki T, Sassa H, Suzuki T, Taniko K, Makino M, et al. Pharmacological properties of fidarestat, a potent aldose reductase inhibitor, clarified by using sorbitol in human and rat erythrocytes. Pharmacology. 2000;62:193–199
  19. Srivastava SK, Hair GA, Das B. Activated and unactivated forms of human erythrocyte aldose reductase. Proceedings of the National Academy of Sciences of the United States of America. 1985;82:7222–7226
  20. The DCCT Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine. 1993;329:977–986
  21. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus . Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183–1197
  22. The UK Prospective Diabetes Study (UKPDS) Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–853

PII: S1056-8727(04)00037-6

doi: 10.1016/j.diacomp.2004.04.003

Journal of Diabetes and Its Complications
Volume 18, Issue 6 , Pages 336-342 , November 2004

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