Kidney drug metabolizing activities in streptozotocin diabetic rats

1. 1. Streptozotocin-induced diabetes produced significant changes on the drug metabolizing enzyme machinery of rat kidney microsomes. 2. 2. It reduced the cytochrome P-450 content by 30%, this effect being reversed by insulin therapy. 3. 3. Total androstenedione oxidative metabolism was increased 2.5-fold and insulin treatment partially antagonized this activation. 4. 4. Total testosterone hydroxylase activities were not modified by diabetes nor by insulin but the formation of 2α OH testosterone and 6β OH testosterone were distinct in diabetes or insulin treated diabetic rats. 5. 5. Only UDP-glucuronyltransferase activity for PNP was found in kidney microsomes. Diabetes determined a lower UDPGT substrate efficiency not reversed by insulin therapy. © 1995

Comparison of alloxan and streptozotocin induced diabetes in rats: Differential effects on microsomal drug metabolism

1. Liver microsomes from alloxan or streptozotocin diabetic rats displayed differential drug metabolizing abilities in vitro. 2. Only streptozotocin liver microsomes exhibited changes in the cytochrome P-450 normal spectral characteristics. 3. Overall testosterone metabolism was significantly increased in streptozotocin diabetic liver microsomes, whereas it was markedly decreased in alloxan diabetes. Mixed function oxidase activity for aminopyrine was similar. 4. Glucuronidation reaction rates towards morphine, oestrone and p-nitrophenol were also markedly distinct in both models as well as after insulin treatment. 5. Results suggest that diabetogenic agents modify sex related isoenzymes of cytochrome P-450 differently and selectively reduce the synthesis of certain UDP-glucuronyltransferase forms. © 1993

Diabetes in female rats; changes in liver microsomal aminopyrine N-demethylase and UDP-glucuronyl transferase activities

Short or long term diabetes in female rats produced remarkable activation of aminopyrine N-demethylation, inhibition of oestrone and p-nitrophenol glucuronidation and no changes in morphine UDP-glucuronyltransferase activity in vitro. Km and Vmax for these reactions were determined. Insulin treatment partially antagonized diabetes activation of aminopyrine N-demethylation: it restored decreased UDP-glucuronyltransferase activities for oestrone and p-nitrophenol only in long term and short term diabetes, respectively. Insulin also markedly inhibited morphine glucuronidation. Triton X-100 also displayed a differential pattern of activation for the glucuronidation reactions in liver microsomes of diabetic rats. Results suggest that diabetes in female rats may increase the actual amount of enzyme protein for aminopyrine metabolism and to decrease that for oestrone and p-nitrophenol

Inhibition and activation of UDP-glucuronyltransferase in alloxanic-diabetic rats

Short or long term alloxan diabetes produced activation of oestrone and morphine glucuronidation and inhibition of p-nitrophenol glucuronidation in rat liver microsomes. Insulin treatment restored decreased glucuronyltransferase (GT) activity for p-nitrophenol and it did not abolish diabetes activation on oestrone glucuronidation. Triton X-100 detergent activation reduced differences between normal, diabetic and insulin treated rats in the glucuronidation rates of the substrates assayed. 1,4-Benzodiazepines inhibited morphine GT activity and stimulated oestrone GT activity in normal, diabetic and insulin treated diabetic rats. Activation and inhibition of GT activities for oestrone and xenobiotics in diabetes mellitus appears to be related with membrane perturbations of liver microsomes