Aldose reductase inhibition and thephosphorus-31 profile of the intact diabetic rat lens

Diabetic metabolic change and response to aldose reductase inhibition in the Wistar rat lens were examined with phospho-rus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy. To avoid artifacts in sample preparation, we used freshly excised lenses and acquired NMR data for 20 min immediately after lens extraction. The results showed a diabetes-induced time-dependent loss of ATP and phosphorylcholine (PC), an increase in a-glycerophosphate (ct-GP) and inorganic phosphate and the appearance of sorbitol-3-phosphate (S-3-P) and fructose-3-phosphate (F-3-P). Oral but not topical dosing of an aldose reductase inhibitor, 5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione, resulted in a positive dose-response correlation characterized by a restoration of PC, S-3-P and F-3-P to the prediabetic level; however, a-GP and ATP were only partially normalized. The significance of the 31P change was further discussed.