Document Detail

Inhibition of sorbitol dehydrogenase. Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats.
MedLine Citation:
PMID:  7859946     Owner:  NLM     Status:  MEDLINE    
These experiments were undertaken to assess the role of sorbitol dehydrogenase in mediating sorbitol pathway-linked neural and vascular dysfunction in rats with streptozocin-induced diabetes. 2-methyl-4-[N,N-dimethylsulfamoyl-piperazino]-pyrimidine (S-0773), a putative inhibitor of sorbitol dehydrogenase, was given in the drinking water to control and diabetic rats. After 5 weeks of diabetes, glycosylated hemoglobin levels were increased twofold and were unaffected by S-0773. Sorbitol levels in diabetic rats were increased 11- to 14-fold in ocular tissues and sciatic nerve; S-0773 increased sorbitol levels another 4-fold or more in these same tissues but had much smaller effects in other tissues. Diabetes-associated increases in fructose levels and lactate:pyruvate ratios in retina and in sciatic nerve were markedly attenuated by S-0773. S-0773 also attenuated, but did not completely normalize, impaired caudal nerve conduction and vascular dysfunction in ocular tissues, sciatic nerve, and aorta in diabetic rats. These observations, together with other evidence, suggest that sorbitol pathway-linked vascular dysfunction (in ocular tissues, peripheral nerve, and aorta) and electrophysiological dysfunction (in peripheral nerve) induced by diabetes are more closely linked to increased oxidation of sorbitol to fructose than to putative osmotic effects of elevated sorbitol levels or redox and metabolic imbalances associated with reduction of glucose to sorbitol by aldose reductase.
R G Tilton; K Chang; J R Nyengaard; M Van den Enden; Y Ido; J R Williamson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Diabetes     Volume:  44     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-03-21     Completed Date:  1995-03-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  234-42     Citation Subset:  AIM; IM    
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.
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MeSH Terms
Diabetes Mellitus, Experimental / physiopathology*
Diabetic Angiopathies / etiology*,  physiopathology
Diabetic Neuropathies / etiology*,  physiopathology
Eye / metabolism
Fructose / metabolism
Hemoglobin A, Glycosylated / metabolism
L-Iditol 2-Dehydrogenase / antagonists & inhibitors*
Lactates / metabolism
Lactic Acid
Pyrimidines / pharmacology*
Pyruvates / metabolism
Pyruvic Acid
Rats, Sprague-Dawley
Retina / metabolism
Sciatic Nerve / metabolism
Sorbitol / metabolism
Grant Support
Reg. No./Substance:
0/Hemoglobin A, Glycosylated; 0/Lactates; 0/Pyrimidines; 0/Pyruvates; 0/S 0773; 127-17-3/Pyruvic Acid; 30237-26-4/Fructose; 50-21-5/Lactic Acid; 50-70-4/Sorbitol; EC 2-Dehydrogenase

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