Summary. The capacities of rat lens and retina to accumulate sorbitol pathway intemiediates in streptozotocin induced diabetes were inve.stigated. The experiments performed were of two types:(i) investigations of the time course of the appearance of the pathway intermediates in lens and retina following the induction of diabetes, and (ii) investigation of the relationship of scirbitol pathway intermediate accumulations to varying doses of .strt'ptozotocin. The experimental objectives were to investigate the factors which control the activity of the pathway in vivo, and to a.ssfss the proposed relation.ship between sorbitol metabolism in the retina and the pathogenesis of diabetic small vessel disease in this tissue.The sorbitol which accumulated in the retina of the diabetic animal (approximately 1-5 iimolc/g protein) was formed by the intrinsic metabolic activity of the tissne and was not attributed to transport from an external metabolic site. The accunmlation of this intermediate was directly related to the plasma gincose concentration and could not be related to other parameters of the diabetic state, e.g. plasma free fatty acid concentration, ketonaemia.It was confirmed that the rat lens accumulated sorbitol (approximately 80 (imole/g protein) and fructose (approximately 20 n'Tiole/g protein) in diabetes, and that such accumulations were related to the glucose concentration of the aqueous humour. The possibility that factors associated with kctoacidosis aflected the relati\e concentration.s of lens sorbitol and fructose was suggested by the results.An hypothesis which invoked sorbitol iiccuninlation to osmotically signifieant concentrations within the retina as a pathogenic agent in diabetic small ve.ssel disease in this tissue conld not be directly supported by the results. Alternate mechanisms by which low concentrations of sorbitol iu diabetic retina could act as a pathogenic stimulus are discussed.
Summary. A series of in vivo and in vitro investigations was perfonned to examine the localisation of sorbitol pathway activity in the rat renal cortex and to investigate the possible relation that the accumulation of sorbitol pathway intermediates in renal cortical tissue may have to the pathogenesis of renal complications in diabetes mellitus.Neither of the sorbitol pathway intermediates, sorbitol or fructose, were detected either in intact glomeruli which had been isolated from rats rendered chronically diabetic with streptozotocin, or in metabolically active glomeruli which had been incubated in vitro in high glucose media. Such data agreed with previously published observations that the enzyme aldose reductase is not present in renal glomeruli, and suggested that changes in sorbitol pathway activity cannot be directly related to the pathogenesis of diabetic glomerulosclerosis.Sorbitol was detected in low concentrations (3-1 nmol/g protein) in cortical tubules which had been isolated from the renal cortex of rats rendered chronically diabetic with streptozotocin. This concentration of sorbitol was higher than that in the intact renal cortex of the diabetic animal (0-3 nmol/g protein) or in the cortical tubules of non-diabetic animals (0 5 (imol/g protein).It is apparent that the renal cortical tubule is a major site of sorbitol pathway activity in the renal cortex. However, there is presently no obvious causal relationship between the accumulation of such relatively low concentrations of sorbitol in the renal cortical tubule and the pathogenesis of glomerulosclerosis or cortical tubular lesions in diabetes.'Present address:
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