The effect of high glucose and oxidative stress on lens metabolism, aldose reductase, and senile cataractogenesis.
Diabetic cataractogenesis, a multifactorial process, was examined with nuclear magnetic resonance (NMR). P-31 NMR spectroscopic studies showed substantial alteration of both energy and membrane metabolism in the diabetic lens. Findings from a C-13 NMR spectroscopic determination of the sorbitol pathway flux in lenses incubated in 35.5 mmol/L glucose revealed that (1) one-third of total glucose consumed was channeled through this pathway, and (2) the turnover rate of NADPH to NADP was 3,000%/hr. Furthermore, a competition for NADPH between aldose reductase and glutathione reductase was demonstrated. It is important to note that all metabolic changes in hyperglycemic/diabetic lenses can be prevented by aldose reductase inhibitors, eg, sorbinil.
Cheng
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González
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D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002386:Cataract / Q000209:etiology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D048909:Diabetes Complications; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005994:Glycerophosphates / Q000032:analysis; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000032:analysis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013012:Sorbitol / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000378:metabolism*
D005994:Glycerophosphates; D007093:Imidazoles; D048289:Imidazolidines; D013012:Sorbitol; D009249:NADP; D000255:Adenosine Triphosphate; C029620:alpha-glycerophosphoric acid; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil; D005947:Glucose