Sorbitol/fructose metabolism in the lens

The function of the sorbitol pathway, both as a secondary energy source and as an osmotic counterbalancing force, was examined. Rat lenses were incubated in media containing fructose as the primary exogenous energy source, and 31P nuclear magnetic resonance (NMR) spectra were accumulated. Fructose was found to be a sub-optimal but usable substrate for glycolysis. The utilization of fructose was further confirmed by a 14C fructose tracer study, using high-pressure liquid chromatography. Thus the intralenticular pool of sorbitol + fructose could serve as a secondary energy source during severe hypoglycemia in the diabetic lens. However, fructose is not a physiologically significant alternative to glucose. 13C NMR spectroscopy was employed to determine the kinetics of sorbitol/fructose accumulation in lenses incubated in 35.5 mM 13C1-glucose, and the sorbitol/fructose consumption after the preincubated lenses were transferred to media containing no glucose. Based on these kinetic studies, we concluded that the sorbitol pathway cannot generate sorbitol/fructose fast enough to offset increased osmotic pressure from high glucose levels in the aqueous humor of the diabetic eye. The contribution of osmotic equivalents from sorbitol + fructose, however, cannot be ignored.