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

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

“…A decrease of UDPGT activities for GT I substrates such as p-nitrophenol and l-naphton but not for GT2 substrates has been described in liver microsomes of diabetic male rats (4). On the contrary, morphine and oestrone glucuronidation appear to be increased in diabetic male rats (6). Results reported here show that in female diabetic rats UDPGT activity for p-nitrophenol was decreased as in male diabetic rats.…”

“…In streptozotonic-induced diabetic mice p-nitrophenol glucuronidation has been shown to be unmodified and Box 70086, Santiago 7 Chile bilirubin glucuronidation increased (5). We have reported that liver rnicrosomes from alloxan diabetic male rats display decreased activity in response to hydroxylate testosterone (9) and p-nitrophenol glucuronidation (6). In contrast UDPGT activities for the glucuronidation of morphine and oestrone were markedly increased (6).…”

“…We have reported that liver rnicrosomes from alloxan diabetic male rats display decreased activity in response to hydroxylate testosterone (9) and p-nitrophenol glucuronidation (6). In contrast UDPGT activities for the glucuronidation of morphine and oestrone were markedly increased (6). An alteration in the membrane enviroment of UDP-glucuronyltransferase rather than a deficiency of this enzyme has been postulated to explain the low UDPGT activities observed in diabetes (4).…”

“…Experimental diabetes in the rat gives rise to a number ofalterations in the activity of the hepatic drug metabolizing enzymes, both in microsomal monooxygenases of the cytochrome P-450 (l ,2,3) and in glucuronidation reactions catalyzed by UDPGlucuronyltransferase (UDPGl) (4,5,6).…”

Disposition of lorazepam in diabetes: differences between patients treated with beef/pork and human insulins

“…Glycosylation of proteins results in perturbation of membrane structure and function, and there is unbridled lipolysis and other, more subtle, changes in intermediary metabolism. Of particular interest to our laboratory has been the observation that the glucuronate-xylulose pathway is abnormal in the tissues of diabetic animals [1][2][3], and that the glucuronidation of drugs and various other substances may be altered in the diabetic-state [4][5][6][7][8][9][10]. Unfortunately, experiments examining drug metabolism in human diabetes have yielded somewhat variable results [11][12][13][14][15][16][17], and there are no unifying hypotheses linking these observations or the findings in animals.…”