Increased urinary prostaglandin excretion in galactose-fed rats.
Increased renal production of prostaglandins (PG) may contribute to the hyperfiltration that accompanies early diabetes. It was postulated 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-PGF1 alpha were studied, using the galactose-fed rat model. UER of PGE2 and 6-keto-PGF1 alpha were measured in three groups of weanling Wistar 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 less than .001) and 6-keto-PGF1 alpha (P less than .01) were higher in group 2 than in group 1. UER of PGE2 (NS) and 6-keto-PGF1 alpha (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-PGF1 alpha. This phenomenon may contribute to the glomerular hyperfiltration of early diabetes.
Zager
P G
PG
University of New Mexico, Albuquerque.
Eaton
R P
RP
Frey
H J
HJ
Scavini
M
M
Jackson
J E
JE
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D004040:Dietary Carbohydrates / Q000494:pharmacology; D015232:Dinoprostone / Q000652:urine*; D005690:Galactose / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D004040:Dietary Carbohydrates; D007093:Imidazoles; D048289:Imidazolidines; D015121:6-Ketoprostaglandin F1 alpha; D000449:Aldehyde Reductase; C026411:sorbinil; D015232:Dinoprostone; D005690:Galactose