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Effect of statil on kidney structure, function and polyol accumulation in diabetes mellitus

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Abstract

We examined the effects of an aldose-reductase inhibitor, statil, which blocks the conversion of glucose to sorbitol, in rats rendered diabetic with streptozotocin in order to determine whether the anticipated changes in sorbitol content was associated with beneficial lack of changes in renal morphology and function. Groups of diabetic, insulin-treated and untreated rats were fed statil daily for a period of five months; each group was paired with a non-drug-treatment control group. At the conclusion of the study period, statil was not found to affect renal sorbitol concentrations nor did it effect functional or structural changes seen in the kidney. We conclude that further study, using other doses of statil and longer duration over which data is collected, must be undertaken in order to implicate the polyol pathway in the renal complications of diabetes mellitus.

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References

  1. 1.

    Srivastava SK, Ansari NH, Hair GA, Das B: Aldose and aldehyde reductases in human tissues. Biochem Biophys Acta 800:220–227, 1984

  2. 2.

    Kinoshita JH: Mechanisms initiating cataract formation. Invest Ophthal 13:713–724, 1974

  3. 3.

    Sredy J, Flam BR, Sawiki DR: Adinpine triphosphatase activity in sciatic nerve tissue of streptozotocin-induced diabetic rats with and without high dietary sucrose: Effect of aldose reductase inhibitors. Proc Soc Exp Biol Med 197:135–143, 1991

  4. 4.

    Gonzalez RG, Barnett P, Aguayo J, Cheng H-M, Chylack LT: Direct measurement of polyol pathway activity in the ocular lens. Diabetes 33:196–199, 1984

  5. 5.

    Schmidt RE, Plurad SB, Sherman WR, Williamson JR, Tilton RG: Effects of aldose reductase inhibitor sorbinil on neuroaxonal dystrophy and levels of myo-inositol and sorbitol in sympathetic autonomic ganglia of streptozocin-induced diabetic rats. Diabetes 38:569–579, 1989

  6. 6.

    Stribling D, Mirrlees DJ, Harrison HE, Earl DCN: Properties of ICI 128,436, a novel aldose reductase inhibitor, and its effects on diabetic complications in the rat. Metabolism 34:336–344, 1985

  7. 7.

    Yatscoff RW, Tevaarwerk GJM, Clarson CL, Warnock LM: Evaluation of the affinity chromatographic procedure or the determination of glycosylated hemoglobin (HbA1). Clin Biochem 16:291–295, 1983

  8. 8.

    Fabing DL, Ertingshausen G: Automated reaction-rate method for the determination of serum creatinine with the cintrifichem. Clin Chem 17:696–699, 1971

  9. 9.

    Chaney AL, Marbach EP: Modified reagents for determination of urea and ammonia. Clin Chem 8:130–132, 1962

  10. 10.

    Bergmeyer HU, Gruber W, Gutman I: Enzymatic analysis. In: HU Bergmeyer (ed.) Vol. 3. Verlag Chemie, Weinheim, Academic Press Inc, New York, London, 1974, pp 1323–1326

  11. 11.

    Sokal RR, Rolf FJ: Biometry. In: Principles and Practices of Statistics in Biological Research. San Francisco, Freeman, 1984

  12. 12.

    Knowles HL, Guest GM, Lampe J, Kessler M, Skillman TG: The course of juvenile diabetes treated with measured diet. Diabetes 14:239–273, 1975

  13. 13.

    Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T: Diabetic nephropathy in Type 1 (insulin-dependent) diabetes: An epidemiological study. Diabetologia 25:496–501, 1983

  14. 14.

    Brown DM, Andres GA, Hostetter TH, Mauer SM, Price R, Ventkatachalan MA: Kidney complications. Diabetes 31 (Suppl. 1): 71–81, 1982

  15. 15.

    Varma S: Aldose reductase and the etiology of diabetic cataracts. Current Topics of Eye Research 3:91–155, 1980

  16. 16.

    Gabby KH: Role of sorbitol pathway in neuropathy. Adv Metab Disord (Suppl. 2): 417–424, 1973

  17. 17.

    Hutton JC, Schofield PJ, Williams JF, Hollows FC: The localization of sorbitol pathway activity in the rat renal cortex and its relationship to the pathogenesis of renal complications of diabetes mellitus. Aust J Exp Biol Med Sci 53:49–57, 1975

  18. 18.

    Beyer-Mears A, Ku L, Cohen MP: Glomerular polyol accumulation in diabetes and its prevention by oral sorbinil. Diabetes 33: 604–607, 1984

  19. 19.

    Gonzalez A-M, Sochor M, McLean P: The effect of an aldose reductase inhibitor (sorbinil) on the level of metabolites in lenses of diabetic rats. Diabetes 32:482–485, 1983

  20. 20.

    Tomlinson DR, Holmes PR, Mayer JH: Reversal by treatment with aldose reductase inhibitor, of impaired axonal transport and motor nerve conduction velocity in experimental diabetes mellitus. Neurosci Lett 31:189–193, 1982

  21. 21.

    Fukushi S, Merola LO, Kinoshita H: Altering the courses of cataracts in diabetic rats. Invest Ophthal Vis Sci 19:313–315, 1980

  22. 22.

    Brown DM, Andres GA, Hostetter TH, Mauer SM, Price R, Ventkatachalan MA: Kidney complications. Diabetes 31 (Suppl. 1): 71–81, 1982

  23. 23.

    Osterby R: Structural changes in the diabetic kidney. Clin Endo Metab 15:733–751, 1986

  24. 24.

    Chang WP, Dimitriodis E, Allen T, Dunlop ME, Cooper M, Larkins RG: The effect of aldose reductase inhibitors on glomerular prostaglandin production and urinary albumin excretion in experimental diabetes mellitus. Diabetologia 34:225–231, 1991

  25. 25.

    Daniels BS, Hostetter TH: Aldose reductase inhibition and glomerular abnormalities in diabetic rats. Diabetes 38:981–986, 1989

  26. 26.

    Korner A, Celsi G, Eklof A-C, Linne T, Perrson B, Aperia A: Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats. Diabetologia 35:414–418, 1992

  27. 27.

    Mauer SM, Steffes MW, Azar S, Brown DM: Effects of sorbinil on glomerular structure and function in long-term-diabetic rats. Diabetes 38:839–846, 1989

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Correspondence to Gregg Faiman.

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Faiman, G., Ganguly, P., Mehta, A. et al. Effect of statil on kidney structure, function and polyol accumulation in diabetes mellitus. Mol Cell Biochem 125, 27–33 (1993). https://doi.org/10.1007/BF00926831

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Key Words

  • diabetes mellitus
  • sorbitol
  • polyol pathway
  • kidney