*2.3. BCRP*

BCRP, expressed at the canalicular membrane of hepatocytes, is also involved in the biliary excretion of its substrates. Altered expressions of hepatic BCRP under diabetic status are dependent on the type of diabetes, and diabetic progression. For example, expressions of hepatic BCRP mRNA in 5-week and 8-week diabetic rats induced by STZ were significantly downregulated, but expression of BCRP protein only showed a trend to decrease [19]. Similarly, He et al. reported that hepatic BCRP mRNA level was decreased in STZ-induced diabetic rats, whereas in type 2 diabetic patients and Goto-Kakizaki (GK) rats BCRP mRNA expression was significantly increased, although BCRP protein was unaltered [20]. Decreased expression of hepatic BCRP protein was observed in 10-day (but not 22-day) diabetic rats induced by STZ/HFD [11]. Interestingly, pregnancy also affected the expression of hepatic BCRP under diabetic status. For example, STZ treatment upregulated the expression of BCRP mRNA and protein in non-pregnant mice, but not in pregnant mice [21].
