Glucuronic acid conjugation by hepatic microsomal fractions isolated from streptozotocin-induced diabetic rats.
The hepatic glucuronidation of 1-naphthol and 4-nitrophenol (3-methylcholanthrene inducible substrates of glucuronyltransferase, GT 1) was found to be deficient in freshly prepared untreated "native" microsomes from streptozotocin-induced diabetic male rats. The defect was not observed in female rats. Moreover, the glucuronidation of 1-naphthol and 4-nitrophenol was higher in "native" microsomes from male control rats than in those from female controls. This sex difference in the glucuronidation of the GT 1 substrates was abolished by detergent activation of the transferase enzyme in vitro. Streptozotocin treatment did not alter the glucuronidation of paracetamol or phenolphthalein (phenobarbitone inducible substrates for GT 2). This diabetes-induced defect in the glucuronidation of GT 1 substrates was abolished by insulin treatment of the animals and was diminished or completely abolished by detergent activation of the transferase enzyme in vitro. Increased membrane constraint is proposed as the mechanism responsible for the transferase defect. 3-Methylcholanthrene induction abolished the streptozotocin-induced defect in 4-nitrophenol glucuronidation, whereas phenobarbitone did not. This is attributed to the differential effect of these inducers on the microsomal membrane.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004789:Enzyme Activation; D004790:Enzyme Induction; D005260:Female; D005965:Glucuronates / Q000302:isolation & purification; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D005965:Glucuronates; D007328:Insulin; D008748:Methylcholanthrene; D014453:Glucuronosyltransferase; D010634:Phenobarbital