MANIPULATING RAT LENS GLUCOSE-METABOLISM WITH EXOGENOUS SUBSTRATES

Diabetic lens glucose metabolism in vivo can be altered by a number of exogenous substrates. We have chosen two, one a glucose epimer (manno se) and the other a glycolytic intermediate (pyruvate), to demonstrate the possibility of this approach. D(+)-Mannose is a D(+)-glucose epim er but in lenses incubated in 35.5 mM mannose, no mannitol (the sorbit ol equivalent) was detected, while both lactate production and P-31 pr ofile appeared normal. Mannose therefore is a good glucose substitute causing no polyol formation. Mannose metabolism in the rat lens in viv o was then examined. Diabetic rats fed mannose-enriched diet over a pe riod of 14 days showed retardation of changes in P-31 metabolites, spe cifically the levels of phosphorylcholine and glycerophosphorylcholine , suggesting a protective effect. Rat lenses incubated in 35.5 mM gluc ose in the presence of 5 mM pyruvate (pyr) showed 50% lower sorbitol t han without pyr. With 5 mM pyr in the drinking water, i.e. pretreatmen t in vivo during a 3-day diabetes induction period, the diabetic rat l ens accumulated acetate and alanine when incubated in the presence of pyr. The decrease in sorbitol was most likely due to a lower glucose n ux rather than an increased polyol dehydrogenase activity, Increasing glucose concentration from 5.5 to 35.5 mM or provision of exogenous py r both caused an intermediate increase in O-2 consumption in the norma l lens; a maximal activity was reached with both 35.5 mM glucose and 5 mM pyruvate in the incubating medium. In the diabetic lens, O-2 consu mption could reach the intermediate but not the maximal level. Dietary pyr pre-treatment also prevented normal and diabetic lenses from maxi mal pyr-stimulated O-2 consumption. The NMR and O-2 consumption data t ogether indicated activation of alanine dehydrogenase and saturation o f Krebs cycle. It appears that dietary supplement of mannose can prese rve P-31 membrane metabolites in the diabetic lens. Mannose can be use d in conjunction with hypoglycemic therapy for the management of diabe tic cataract. In addition, pyruvate may be effective in enhancing lens energy metabolism and lower sorbitol production. (C) 1995 Academic Pr ess Limited