To investigate the aetiology of complications secondary to experimental diabetes in the rat, the concentrations of
glucose,
sorbitol,
fructose,
fructose-1-phosphate,
lactate and
inositol were measured in the retina and sciatic nerve of
streptozotocin-diabetic and normal rats treated for 22 days with
ICI 105552 (1-(3,4-dichlorobenzyl)-3-methyl-1,2-dihydro-2-oxoquinol-4-ylacetic
acid,
sodium salt; 50 mg/kg body wt daily), an inhibitor of
aldose reductase (E.C. 1.1.1.21) the first
enzyme of the
sorbitol pathway. In the diabetic nerve, where accumulation of
sorbitol may be pathogenic, treatment with
ICI 105552 reduced the accumulations of
sorbitol (70%),
fructose (47%) and
lactate (34%) without affecting
glucose,
fructose-1-phosphate or
inositol. In the nerves of controls, the inhibitor reduced both
sorbitol (23%) and
fructose (20%) levels without other effects. In the diabetic retina where accumulation of
sorbitol or
lactate might be pathogenic, treatment with
ICI 105552 had no statistically significant effect upon the concentrations of
glucose,
sorbitol,
fructose,
fructose-1-phosphate or
inositol. However, the inhibitor reduced the concentration of
lactate to below the non-diabetic level. In the retinas of controls, dosage with
ICI 105552 reduced the concentration of
sorbitol by 36% without other effects.
THE RESULTS: