TISSUE ASCORBIC-ACID AND POLYOL PATHWAY METABOLISM IN EXPERIMENTAL DIABETES

Previous studies demonstrating reduced plasma concentrations of ascorb ic acid (AA) in diabetes and interactions between this vitamin and bio chemical mechanisms such as synthesis of structural proteins, oxidativ e stress, polyol pathway and non-enzymatic glycation of proteins sugge st that disturbed AA metabolism may be important in the pathogenesis o f diabetic microangiopathy. However, limited information is available on the concentration of AA in tissues which develop diabetic complicat ions. This study demonstrates reduced renal but not sciatic nerve or p lasma AA concentration in two animal models of insulin-dependent diabe tes mellitus, namely the STZ-diabetic rat and the spontaneously diabet ic BE rat. Decreased lens AA concentration was also observed in STZ-di abetic rats. Improvement of glycaemic control by insulin treatment (al beit insufficient to achieve normoglycaemia) partially corrected lens and renal AA concentration in STZ-diabetic rats. AA treatment increase d kidney and lens AA concentrations of STZ-diabetic and non-diabetic r ats and corrected the abnormalities observed for untreated diabetic ra ts. Sciatic nerve AA concentration was not increased by AA treatment i n any group. Tissue ratios of dehydroascorbic acid (DHAA)/AA, one inde x of oxidative stress, were not different between the diabetic and non -diabetic groups and were unaltered by BA supplementation. AA treatmen t of STZ-diabetic rats had no effect on elevated tissue concentrations of glucose, sorbitol and fructose or reduced myo-inositol concentrati on. The effect of reduced tissue AA levels in diabetes on either colla gen synthesis or ability to combat increased free radical production i s not known. However, correction of abnormal kidney and lens AA concen trations in experimental diabetes by AB supplementation suggests that if AA does have a role in the development or progression of the renal and ocular complications of diabetes, this treatment could be benefici al.