Polyol pathway activity in streptozotocin-diabetic rat lens

We have examined polyol pathway kinetics in the lenses of rats made diabetic with streptozotocin. At up to 11 days after diabetes induction, the lenses were isolated and subjected to 'pulse-chase' studies: the lenses were incubated with [13C]glucose and lens metabolism followed by [13C]nuclear magnetic resonance (NMR) spectroscopy. Proton NMR spectroscopy was also performed to measure the hexose monophosphate shunt (HMPS) activity. The results showed that (1) the activity of aldose reductase increased initially and decreased after 11 days of diabetes; (2) the fructose pool increased initially but started to decline after 3 days; (3) the HMPS activity increased nearly 40% immediately after diabetes induction; and (4) the turnover rates of glucose, alpha-glycerophosphate (GP), lactate, sorbitol, and fructose were 80.8 +/- 2.6, 10.1 +/- 1.4, 47.7 +/- 3.7, 7.9 +/- 0.9 and 5.2 +/- 2.2 nmol hr-1 lens-1 (34 mg wet weight lens-1), respectively. Up to 35% of lactate appeared to derive from the polyol pathway. Further, GP was rapidly metabolized, although its fate is currently unknown. These results reveal a far more complex pattern of glucose metabolism in the diabetic lens than that in lenses incubated in high glucose.