*2.4. MRP2*

MRP2 is co-expressed with P-gp and BCRP at the canalicular membrane of hepatocytes. Alterations in the expression of MRP2 by diabetes are also dependent on species. STZ-induced diabetic Donryu rats showed significantly lower expression of hepatic MRP2 mRNA, which was in line with lower biliary excretion of pravastatin [13]. A similar decrease in the protein (not mRNA) of hepatic MRP2 was found in STZ-induced diabetic male Wistar rats [22]. However, STZ-induced diabetic Sprague-Dawley rats showed higher expression of hepatic MRP2 protein, which was in line with higher biliary excretion of sulfobromophthalein compared with control rats [23]. Moreover, STZ treatment upregulated the expression of MRP2 in non-pregnant mice but not in pregnant mice [21]. The induction of hepatic MRP2 may partly explain the increased biliary excretions of cefoperazone and some anions (such as bengal, indocyanine green and bromcresol green) under diabetic status [24,25].
