Molecular basis of bilirubin UDP-glucuronosyltransferase induction in spontaneously diabetic rats, acetone-treated rats and starved rats

The co-ordinated induction of several hepatic drug-metabolizing enzymes is a common feature in the regulation of drug biotransformation under normal a nd pathological conditions. In the present study the activity and expressio n of bilirubin UDP-glucuronosyltransferase (UGT1A1) were investigated in li vers of BioBreeding/Worcester diabetic, fasted and acetone-treated rats. Bi lirubin glucuronidation was stimulated by all three treatments; this was co rrelated with an increase in the UGT1A1 protein concentration in hepatic mi crosomes. Transcriptional induction of UGT1A1 was also observed in diabetes and starvation but not with acetone treatment, which apparently caused tra nslational stabilization of the enzyme protein. The hormonal/metabolic alte rations in diabetes and starvation might be a model for postnatal developme nt. The sudden interruption of maternal glucose supply signals the enhanced expression of UGT1A1, giving a novel explanation for the physiological ind uction of bilirubin glucuronidation in newborn infants.