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Titolo:
ELEVATED GLUCOSE-LEVELS INCREASE RETINAL GLYCOLYSIS AND SORBITOL PATHWAY METABOLISM - IMPLICATIONS FOR DIABETIC-RETINOPATHY
Autore:
VANDENENDEN MK; NYENGAARD JR; OSTROW E; BURGAN JH; WILLIAMSON JR;
Indirizzi:
WASHINGTON UNIV,SCH MED,DEPT PATHOL,BOX 8118,660 S EUCLID AVE ST LOUIS MO 63110 WASHINGTON UNIV,SCH MED,DEPT PATHOL ST LOUIS MO 63110 ACAD ZIEKENHUIS,MIDDELHEIM HOSP,DEPT INTERNAL MED ANTWERP BELGIUM AARHUS UNIV,STEREOL RES LAB AARHUS C DENMARK
Titolo Testata:
Investigative ophthalmology & visual science
fascicolo: 8, volume: 36, anno: 1995,
pagine: 1675 - 1685
SICI:
0146-0404(1995)36:8<1675:EGIRGA>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALDOSE REDUCTASE INHIBITORS; VASCULAR AUTO-REGULATION; NITRIC-OXIDE SYNTHASE; BLOOD-FLOW; RAT LENS; CIRCULATION; PREVENTION; MELLITUS; PYRUVATE; COMPLICATIONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
84
Recensione:
Indirizzi per estratti:
Citazione:
M.K. Vandenenden et al., "ELEVATED GLUCOSE-LEVELS INCREASE RETINAL GLYCOLYSIS AND SORBITOL PATHWAY METABOLISM - IMPLICATIONS FOR DIABETIC-RETINOPATHY", Investigative ophthalmology & visual science, 36(8), 1995, pp. 1675-1685

Abstract

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 at37 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. Elevatedglucose 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 acutelyhyperglycemic animals. These findings, together with other observations, suggest that this redox imbalance precedes, and may contribute to,hypoxic and ischemic retinopathy associated with diabetes.

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Documento generato il 28/11/20 alle ore 12:48:54