Document Detail

Elevated glucose levels increase retinal glycolysis and sorbitol pathway metabolism. Implications for diabetic retinopathy.
MedLine Citation:
PMID:  7601647     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To assess effects of elevated glucose levels on retinal glycolysis and sorbitol pathway metabolism. METHODS: Freshly isolated retinas from normal male Sprague-Dawley rats were incubated for 2 hours at 37 degrees C, pH 7.45, in Krebs bicarbonate-Hepes buffer containing 5, 10, 20, or 30 mM glucose. Glycolytic metabolites, sorbitol, and fructose were measured in extracts of retina and medium. RESULTS: Elevated glucose levels increased retinal levels of sorbitol and triose phosphates, decreased sn-glycerol-3-phosphate levels, increased lactate and fructose production, and increased the retinal lactate-pyruvate ratio (indicative of an increased cytosolic ratio of free NADH-NAD+ like that induced by hypoxia). An inhibitor of aldose reductase (AL 4114) normalized sorbitol, fructose, triose phosphates, and the lactate-pyruvate ratio without affecting lactate production or sn-glycerol 3-phosphate levels. CONCLUSIONS: Elevation of retinal glucose levels causes a hypoxia-like redox imbalance "pseudohypoxia" that results from increased oxidation of sorbitol to fructose in the second step of the sorbitol pathway. This redox imbalance provides a plausible explanation for impaired regulation of retinal blood flow (in the absence of vascular structural changes) in humans with diabetes and in nondiabetic acutely hyperglycemic animals. These findings, together with other observations, suggest that this redox imbalance precedes, and may contribute to, hypoxic and ischemic retinopathy associated with diabetes.
M K Van den Enden; J R Nyengaard; E Ostrow; J H Burgan; 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:  Investigative ophthalmology & visual science     Volume:  36     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  1995 Jul 
Date Detail:
Created Date:  1995-08-07     Completed Date:  1995-08-07     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1675-85     Citation Subset:  IM    
Department of Internal Medicine, AZ Middelheim Hospital, Antwerp, Belgium.
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MeSH Terms
Aldehyde Reductase / antagonists & inhibitors
Diabetic Retinopathy / metabolism*
Fluorenes / pharmacology
Fructose / metabolism
Glucose / pharmacology*
Hydantoins / pharmacology
Inositol / metabolism
Lactates / metabolism
Pyruvates / metabolism
Pyruvic Acid
Rats, Sprague-Dawley
Retina / drug effects,  metabolism*
Sorbitol / metabolism*
Spiro Compounds / pharmacology
Grant Support
Reg. No./Substance:
0/Fluorenes; 0/Hydantoins; 0/Lactates; 0/Pyruvates; 0/Spiro Compounds; 127-17-3/Pyruvic Acid; 139911-05-0/AL 4114; 30237-26-4/Fructose; 50-70-4/Sorbitol; 50-99-7/Glucose; 6917-35-7/Inositol; EC Reductase
Comment In:
Invest Ophthalmol Vis Sci. 1997 Jul;38(8):1467-70   [PMID:  9224273 ]

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