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The Polyol Pathway

A Historical Review

  • Section 1 The Polyol Pathway and Complications of Diabetes
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Summary

Polyhydric alcohols (polyols) are widely distributed in nature, and the enzymes of the polyol pathway (aldose reductase and sorbitol dehydrogenase) are present in many mammalian tissues. The function of this pathway remains a mystery. A primary role for the pathway in the pathogenesis of ‘sugar cataract’ was provided by a number of experimental observations and in the 1960s the ‘osmotic hypothesis’ was propounded. This hypothesis also had implications for the pathogenesis of diabetic neuropathy. However, in the 1970s doubts were raised about the validity of the hypothesis, culminating in experiments which suggested that abnormalities in myoinositol metabolism in nerve and lens were more closely related to the glucose-induced functional changes in these tissues than was the polyol pathway. Nevertheless, increased activity of the polyol pathway must still be regarded as an instigator of the biochemical abnormalities that lead to damage of lens and nerve in diabetes mellitus.

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References

  • Gabbay KH. The sorbitol pathway and the complications of diabetes. New England Journal of Medicine 288: 831–836, 1973

    Article  PubMed  CAS  Google Scholar 

  • Greene DA, Lattimer SA. Action of sorbinil in diabetic peripheral nerve relationship of polyol (sorbitol) pathway inhibition to a myo-inositol mediated defect in sodium-potassium ATPase activity. Diabetes 33: 712–716, 1984

    Article  PubMed  CAS  Google Scholar 

  • Hers HG. The mechanism of the formation of seminal fructose and fetal fructose. Biochimica et Biophysica Acta 37: 127–138, 1960

    Article  PubMed  CAS  Google Scholar 

  • Jakobsen J. Axonal dwindling in early experimental diabetes. I. A study of cross sectioned nerves. Diabetologia 12: 539–546, 1976

    Article  PubMed  CAS  Google Scholar 

  • Kinoshita JH, Dvornik D, Draml M, Gabbay KH. The effect of an aldose reductase inhibitor on the galactose-exposed rabbit lens. Biochimica et Biophysica Acta 158: 472–475, 1968

    Article  PubMed  CAS  Google Scholar 

  • Kinoshita JH, Futterman S, Satoh K, Merola LO. Factors affecting the formation of sugar alcohols in ocular lens. Biochimica et Biophysica Acta 74: 340–350, 1963

    Article  PubMed  CAS  Google Scholar 

  • Kuwabara T, Kinoshita JH, Cogan DG. Electron microscopic study of galactose-induced cataract. Investigative Ophthalmology and Visual Science 8: 133–149, 1969

    CAS  Google Scholar 

  • Ludvigson MD, Sorensen RL. Immunohistochemical localization of aldose reductase. II. Rat eye and kidney. Diabetes 29: 450–459, 1980

    Article  PubMed  CAS  Google Scholar 

  • Mayer JH, Tomlinson DR. Prevention of defects of axonal transport and nerve conduction velocity by oral administration of myo-inositol or an aldose reductase inhibitor in streptozotocin-diabetic rats. Diabetologia 25: 433–438, 1983

    Article  PubMed  CAS  Google Scholar 

  • Stewart MA, Kurian MM, Sherman WR, Cotlier EV. Inositol changes in nerve and lens of galactose fed rats. Journal of Neurochemistry 15: 941–946, 1968

    Article  PubMed  CAS  Google Scholar 

  • Stewart MA, Sherman WR, Anthony S. Free sugars in alloxan diabetic rat nerve. Biochemical and Biophysical Research Communications 22: 488–491, 1966

    Article  CAS  Google Scholar 

  • van Heyningen R. The sorbitol pathway in the lens. Experimental Eye Research 1: 396–404, 1962

    Article  Google Scholar 

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Clements, R.S. The Polyol Pathway. Drugs 32 (Suppl 2), 3–5 (1986). https://doi.org/10.2165/00003495-198600322-00003

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  • DOI: https://doi.org/10.2165/00003495-198600322-00003

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