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. 1988 Aug;82(2):624–627. doi: 10.1172/JCI113641

Administration of an aldose reductase inhibitor induces a decrease of collagen fluorescence in diabetic rats.

G Suárez 1, R Rajaram 1, K C Bhuyan 1, A L Oronsky 1, J A Goidl 1
PMCID: PMC303557  PMID: 3136193

Abstract

As a consequence of an increased flux through the sorbitol pathway fructose levels rise in various tissues in diabetes. Also, in vitro nonenzymatic fructosylation of protein induces the generation of fluorescence at a rate 10 times greater than glucosylation. The administration of sorbinil, an aldose reductase inhibitor known to lower tissue fructose concentration, to experimental diabetic rats led to a decrease in the fluorescence related to advanced Maillard products in their skin collagen. This effect is consistent with the in vivo occurrence of nonenzymatic fructosylation of collagen. A potential pathogenetic role for this posttranslational modification in diabetic complications should be considered.

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Selected References

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  1. Ahmed M. U., Thorpe S. R., Baynes J. W. Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. J Biol Chem. 1986 Apr 15;261(11):4889–4894. [PubMed] [Google Scholar]
  2. Brownlee M., Vlassara H., Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med. 1984 Oct;101(4):527–537. doi: 10.7326/0003-4819-101-4-527. [DOI] [PubMed] [Google Scholar]
  3. Cerami A., Stevens V. J., Monnier V. M. Role of nonenzymatic glycosylation in the development of the sequelae of diabetes mellitus. Metabolism. 1979 Apr;28(4 Suppl 1):431–437. doi: 10.1016/0026-0495(79)90051-9. [DOI] [PubMed] [Google Scholar]
  4. Chandrakasan G., Torchia D. A., Piez K. A. Preparation of intact monomeric collagen from rat tail tendon and skin and the structure of the nonhelical ends in solution. J Biol Chem. 1976 Oct 10;251(19):6062–6067. [PubMed] [Google Scholar]
  5. Chung E., Miller E. J. Collagen polymorphism: characterization of molecules with the chain composition (alpha 1 (3)03 in human tissues. Science. 1974 Mar;183(130):1200–1201. doi: 10.1126/science.183.4130.1200. [DOI] [PubMed] [Google Scholar]
  6. Eaton R. P. Aldose reductase inhibition and the diabetic syndrome of limited joint mobility: implications for altered collagen hydration. Metabolism. 1986 Apr;35(4 Suppl 1):119–121. doi: 10.1016/0026-0495(86)90200-3. [DOI] [PubMed] [Google Scholar]
  7. Eaton R. P., Sibbitt W. L., Jr, Harsh A. The effect of an aldose reductase inhibiting agent on limited joint mobility in diabetic patients. JAMA. 1985 Mar 8;253(10):1437–1440. [PubMed] [Google Scholar]
  8. Eaton R. P. The collagen hydration hypothesis: a new paradigm for the secondary complications of diabetes mellitus. J Chronic Dis. 1986;39(10):763–766. doi: 10.1016/0021-9681(86)90078-0. [DOI] [PubMed] [Google Scholar]
  9. Gabbay K. H., Kinoshita J. H. Mechanism of development and possible prevention of sugar cataracts. Isr J Med Sci. 1972 Aug-Sep;8(8):1557–1561. [PubMed] [Google Scholar]
  10. Gabbay K. H., Merola L. O., Field R. A. Sorbitol pathway: presence in nerve and cord with substrate accumulation in diabetes. Science. 1966 Jan 14;151(3707):209–210. doi: 10.1126/science.151.3707.209. [DOI] [PubMed] [Google Scholar]
  11. Heath H., Hamlett Y. C. The sorbitol pathway: effect of streptozotocin induced diabetes and the feeding of a sucrose-rich diet on glucose, sorbitol and fructose in the retina, blood and liver of rats. Diabetologia. 1976 Mar;12(1):43–46. doi: 10.1007/BF01221963. [DOI] [PubMed] [Google Scholar]
  12. Kennedy L., Baynes J. W. Non-enzymatic glycosylation and the chronic complications of diabetes: an overview. Diabetologia. 1984 Feb;26(2):93–98. doi: 10.1007/BF00281113. [DOI] [PubMed] [Google Scholar]
  13. Kinoshita J. H., Fukushi S., Kador P., Merola L. O. Aldose reductase in diabetic complications of the eye. Metabolism. 1979 Apr;28(4 Suppl 1):462–469. doi: 10.1016/0026-0495(79)90057-x. [DOI] [PubMed] [Google Scholar]
  14. Li W., Khatami M., Rockey J. H. The effects of glucose and an aldose reductase inhibitor on the sorbitol content and collagen synthesis of bovine retinal capillary pericytes in culture. Exp Eye Res. 1985 Mar;40(3):439–444. doi: 10.1016/0014-4835(85)90156-3. [DOI] [PubMed] [Google Scholar]
  15. Lorenzi M., Toledo S., Boss G. R., Lane M. J., Montisano D. F. The polyol pathway and glucose 6-phosphate in human endothelial cells cultured in high glucose concentrations. Diabetologia. 1987 Apr;30(4):222–227. doi: 10.1007/BF00270419. [DOI] [PubMed] [Google Scholar]
  16. Monnier V. M., Vishwanath V., Frank K. E., Elmets C. A., Dauchot P., Kohn R. R. Relation between complications of type I diabetes mellitus and collagen-linked fluorescence. N Engl J Med. 1986 Feb 13;314(7):403–408. doi: 10.1056/NEJM198602133140702. [DOI] [PubMed] [Google Scholar]
  17. Morrison A. D., Clements R. S., Jr, Winegrad A. I. Effects of elevated glucose concentrations on the metabolism of the aortic wall. J Clin Invest. 1972 Dec;51(12):3114–3123. doi: 10.1172/JCI107138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Poulsom R., Boot-Handford R. P., Heath H. The effects of long-term treatment of streptozotocin-diabetic rats with an aldose reductase inhibitor. Exp Eye Res. 1983 Nov;37(5):507–515. doi: 10.1016/0014-4835(83)90027-1. [DOI] [PubMed] [Google Scholar]
  19. Poulsom R., Mirrlees D. J., Earl D. C., Heath H. The effects of an aldose reductase inhibitor upon the sorbitol pathway, fructose-1-phosphate and lactate in the retina and nerve of streptozotocin-diabetic rats. Exp Eye Res. 1983 May;36(5):751–760. doi: 10.1016/0014-4835(83)90112-4. [DOI] [PubMed] [Google Scholar]
  20. Rosenbloom A. L., Silverstein J. H., Lezotte D. C., Richardson K., McCallum M. Limited joint mobility in childhood diabetes mellitus indicates increased risk for microvascular disease. N Engl J Med. 1981 Jul 23;305(4):191–194. doi: 10.1056/NEJM198107233050403. [DOI] [PubMed] [Google Scholar]
  21. Stribling D., Mirrlees D. J., Harrison H. E., Earl D. C. Properties of ICI 128,436, a novel aldose reductase inhibitor, and its effects on diabetic complications in the rat. Metabolism. 1985 Apr;34(4):336–344. doi: 10.1016/0026-0495(85)90223-9. [DOI] [PubMed] [Google Scholar]
  22. Tomlinson D. R., Townsend J., Fretten P. Prevention of defective axonal transport in streptozocin-diabetic rats by treatment with "Statil" (ICI 128436), an aldose reductase inhibitor. Diabetes. 1985 Oct;34(10):970–972. doi: 10.2337/diab.34.10.970. [DOI] [PubMed] [Google Scholar]
  23. Tomlinson D. R., Willars G. B., Robinson J. P. Prevention of defects of axonal transport in experimental diabetes by aldose reductase inhibitors. Drugs. 1986;32 (Suppl 2):15–18. doi: 10.2165/00003495-198600322-00005. [DOI] [PubMed] [Google Scholar]
  24. WOESSNER J. F., Jr The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys. 1961 May;93:440–447. doi: 10.1016/0003-9861(61)90291-0. [DOI] [PubMed] [Google Scholar]

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