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Prevention of Defects of Axonal Transport in Experimental Diabetes by Aldose Reductase Inhibitors

  • Section 1 The Polyol Pathway and Complications of Diabetes
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Summary

Experiments on streptozotocin-diabetic rats have indicated that axonal transport of choline acetyltransferase is reduced in sciatic nerve. Treatment with an aldose reductase inhibitor both prevented and reversed this defect which was related to marked accumulations of sorbitol and fructose. Concurrent with these accumulations the content of myo-inositol in diabetic peripheral nerve is depleted. Further experiments taking account of nerve water content showed that the depletion of myo-inositol was ‘real’ not apparent. When the level of myo-inositol was maintained, either by feeding myo-inositol or by the inhibition of aldose reductase, the development of defective axonal transport of choline acetyltransferase and choline-containing lipids was prevented.

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References

  • Clements Jr RS. Diabetic neuropathy: new concepts of its etiology. Diabetes 28: 604–611, 1979

    PubMed  CAS  Google Scholar 

  • Finegold D, Lattimer SA, Nolle S, Bernstein M, Greene DA. Polyol pathway activity and myo-inositol metabolism, a suggested relationship in the pathogenesis of diabetic neuropathy. Diabetes 32: 988–992, 1983

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Gabbay KH, Merola LO, Field RA. Sorbitol pathway: presence in nerve and cord with substrate accumulation in diabetes. Science 151: 209–210, 1966

    Article  PubMed  CAS  Google Scholar 

  • Gillon KRW, Hawthorne JN. Transport of myo-inositol into endoneurial preparations of sciatic nerve from normal and streptozotocin-diabetic rats. Biochemical Journal 210: 775–781, 1983

    PubMed  CAS  Google Scholar 

  • Gillon KRW, Hawthorne JN, Tomlinson DR. Myo-inositol and sorbitol metabolism in relation to peripheral nerve function in experimental diabetes in the rat: the effect of aldose reductase inhibition. Diabetologia 25: 365–371, 1983

    Article  PubMed  CAS  Google Scholar 

  • Greene DA, de Jesus PV, Winegrad AI. Effects of insulin and dietary myo-inositol on impaired peripheral motor conduction velocity in acute streptozotocin diabetics. Journal of Clinical Investigation 55: 1326–1336, 1975

    Article  PubMed  CAS  Google Scholar 

  • Jakobsen J. Peripheral nerves in early experimental diabetes. Expansion of the endoneurial space as a cause of increased water content. Diabetologia 14: 113–119, 1978

    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 

  • Robinson JP, Tomlinson DR. Impaired axonal transport of choline-containing lipids in rats with experimental diabetes mellitus and its prevention by sorbinil, an aldose reductase inhibitor. Journal of Physiology 369: 158P, 1985

  • Tomlinson DR, Mayer JH. Defects of axonal transport in diabetes mellitus — a possible contribution to the aetiology of diabetic neuropathy. Journal of Autonomic Pharmacology 4: 59–72, 1984

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson DR, Mayer JH. Reversal of deficits in axonal transport and nerve conduction velocity by treatment of streptozotocin-diabetic rats with myo-inositol. Experimental Neurology 89: 420–427, 1985

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson DR, Moriarty RJ, Mayer JH. Prevention and reversal of defective axonal transport and motor nerve conduction velocity in rats with experimental diabetes by treatment with the aldose reductase inhibitor sorbinil. Diabetes 33: 470–476, 1984

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson DR, Townsend J, Fretten P. Prevention of defective axonal transport in streptozotocin-diabetic rats by treatment with ‘Statil’ (ICI 128436), an aldose reductase inhibitor. Diabetes 34: 970–972, 1985

    Article  PubMed  Google Scholar 

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Tomlinson, D.R., Willars, G.B. & Robinson, J.P. Prevention of Defects of Axonal Transport in Experimental Diabetes by Aldose Reductase Inhibitors. Drugs 32 (Suppl 2), 15–18 (1986). https://doi.org/10.2165/00003495-198600322-00005

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  • DOI: https://doi.org/10.2165/00003495-198600322-00005

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