Increased renal production of prostaglandins (PG) may contribute to the hyperfiltration that accompanies early diabetes. It was posulated that a putative metabolic abnormality of diabetes, ie, increased flux through the polyol pathway, stimulates renal PG production and that this phenomenon can be prevented by aldose-reductase inhibition. To test this hypothesis, the effects of polyol accumulation on urinary excretion rates (UER) of PGE2 and 6-keto-PGF1α were studied, using the galactose-fed rat model. UER of PGE2 and 6-keto-PGF1α were measured in three groups of weanling Wister male rats. Group 1 was maintained on normal chow (n = 6), group 2 was fed chow supplemented with 30% galactose (n = 6), and group 3 received chow supplemented with 30% galactose and 0.7% sorbinil (n = 6). Ten 24-hour urine samples were obtained from each group between 151 and 240 days on the respective diets. UER of PGE2 (P <.001) and 6-keto-PGF1α (P <.01) were higher in group 2 than in group 1. UER of PGE2 (NS) and 6-keto-PGF1α (NS), respectively, were similar in groups 1 and 3. These data indicate that flux through the polyol pathway modulates the UER of PGE2 and 6-keto-PGF1α. This phemonenon may contribute to the glomerular hyperfiltration of early diabetes.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism