Nerve conduction and aldose reductase inhibition during 5 years of diabetes or galactosaemia in dogs (original) (raw)
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
Summary
To evaluate the role of excessive polyol pathway activity in the pathogenesis of nerve disorders in diabetes mellitus, nerve conduction velocity was measured in motor nerves of diabetic dogs given an aldose reductase inhibitor (Sorbinil) or placebo, and also in non-diabetic dogs made experimentally galactosaemic. The nerve conduction velocity slowly declined in the diabetic placebo group, becoming significantly less than normal by the fifth year of the study, and the decline was prevented by administration of the aldose reductase inhibitor. Non-diabetic dogs made galactosaemic by consuming a 30 % galactose diet developed erythrocyte and nerve polyol concentrations many times greater than that of diabetic or normal animals, but the nerve conduction velocity remained normal throughout 5 years of study. These results in dogs suggest that aldose reductase inhibitors may prevent defective nerve conduction in long-term diabetes, and raise the possibility that excessive accumulation of polyol itself is not sufficient to produce the nerve defect in the absence of excessive polyol utilization.
Access this article
Subscribe and save
- Get 10 units per month
- Download Article/Chapter or eBook
- 1 Unit = 1 Article or 1 Chapter
- Cancel anytime Subscribe now
Buy Now
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Instant access to the full article PDF.
Similar content being viewed by others
References
- McCallum KNC, Sharma AK, Blanchard DS et al. (1986) The effect of continuous subcutaneous insulin therapy on morphological and biochemical abnormalities of peripheral nerves in experimental diabetes. J Neurol Sci 74: 55–67
Article PubMed CAS Google Scholar - Engerman RL, Kern TS, Larson ME (1990) Nerve conduction velocity in dogs is reduced by diabetes and not by galactosaemia. Metabolism 39: 638–640
Article PubMed CAS Google Scholar - Cameron NE, Leonard MB, Ross IS, Whiting PH (1986) The effects of Sorbinil on peripheral nerve conduction velocity, polyol concentrations and morphology in the streptozotocindiabetic rat. Diabetologia 29: 168–174
Article PubMed CAS Google Scholar - Mayer JH, Tomlinson DR (1983) 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
Article PubMed CAS Google Scholar - Yue DK, Hanwell MA, Satchell PM, Turtle JR (1982) The effects of aldose reductase inhibition on nerve conduction velocity in diabetic rats. Diabetes 31: 789–794
Article PubMed CAS Google Scholar - Greene DH, Lattimer SA, Sima AAF (1988) Are disturbances of sorbitol, phophoinositides, and Na+-K+-ATPase regulation involved in pathogenesis of diabetic neuropathy? Diabetes 37: 688–693
Article PubMed CAS Google Scholar - Kim J, Kyriazi H, Greene DA (1991) Normalization of Na+-K+-ATPase activity in isolated membrane fraction from sciatic nerves of streptozotocin-induced diabetic rats by dietary myo-inositol supplementation in vivo or protein kinase C agonists in vitro. Diabetes 40: 558–567
Article PubMed CAS Google Scholar - Lambourne JE, Tomlinson DR, Brown AM, Willars GB (1987) Opposite effects of diabetes and galactosaemia on adenosine triphosphatase in rat nervous tissue. Diabetologia 30: 360–362
Article PubMed CAS Google Scholar - Willars GB, Lambourne JE, Tomlinson DR (1987) Does galactose feeding provide a valid model of consequences of exaggerated polyol-pathway flux in peripheral nerve in experimental diabetes? Diabetes 36: 1425–1431
Article PubMed CAS Google Scholar - Engerman R, Bloodworth J, Nelson S (1977) Relationship of microvascular disease in diabetes to metabolic control. Diabetes 26: 760–769
Article PubMed CAS Google Scholar - Engerman RL, Kern TS (1987) Progression of incipient diabetic retinopathy during good glycaemic control. Diabetes 36: 808–812
Article PubMed CAS Google Scholar - Engerman RL, Kern TS (1984) Experimental galactosaemia produces diabetic-like retinopathy. Diabetes 33: 97–100
Article PubMed CAS Google Scholar - Broderson R, Ricketts HT (1949) Evaluation of a modified Sumner’s method (dinitrosalicylic acid) for determination of glucose in urine. J Lab Clin Med 34: 1447–1456
Google Scholar - Kern TS, Engerman RL (1991) Retinal polyol and myo-inositol in galactosaemic dogs given an aldose reductase inhibitor. Invest Ophthalmol Vis Sci 32: 3175–3177
PubMed CAS Google Scholar - Engerman RL, Kern TS (1993) Aldose reductase inhibition fails to prevent retinopathy in diabetic and galactosaemic dogs. Diabetes 42: 820–825
Article PubMed CAS Google Scholar - Laird NM, Ware JH (1982) Random effects models for longitudinal data. Biometrics 3: 963–974
Article Google Scholar - Sima AAF, Bril V, Nathaniel V et al. (1988) Regeneration and repair of myelinated fibers in sural-nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil. N Engl J Med 319: 548–555
PubMed CAS Google Scholar - Gabbay KH (1973) Role of sorbitol pathway in neuropathy. In: Camerini-Davalos RA, Cole HS (eds) Vascular and neurological changes in early diabetes. Academic Press, New York, pp 417–424
Google Scholar - Calcutt NA, Tomlinson DR, Biswas S (1990) Coexistence of nerve conduction deficit with increased Na+-K+-ATPase activity in galactose-fed mice. Diabetes 39: 663–666
Article PubMed CAS Google Scholar - Sharma AK, Thomas PK, Baker RWR (1976) Peripheral nerve abnormalities related to galactose administration in rats. J Neurol Neurosurg Psych 39: 794–802
Article CAS Google Scholar
Author information
Authors and Affiliations
- Department of Ophthalmology, University of Wisconsin, 1300 University Avenue, 53706, Madison, WI, USA
R. L. Engerman, T. S. Kern & M. E. Larson
Authors
- R. L. Engerman
You can also search for this author inPubMed Google Scholar - T. S. Kern
You can also search for this author inPubMed Google Scholar - M. E. Larson
You can also search for this author inPubMed Google Scholar
Rights and permissions
About this article
Cite this article
Engerman, R.L., Kern, T.S. & Larson, M.E. Nerve conduction and aldose reductase inhibition during 5 years of diabetes or galactosaemia in dogs.Diabetologia 37, 141–144 (1994). https://doi.org/10.1007/s001250050084
- Received: 08 June 1993
- Revised: 26 August 1993
- Issue Date: February 1994
- DOI: https://doi.org/10.1007/s001250050084