*2.2. P-gp*

P-gp, expressed at the canalicular membrane of hepatocytes, mediates biliary excretion of its substrates. Diabetes was reported to upregulate the expression of hepatic Mdr1b (ABCB1b) mRNA and P-gp protein in 8-day diabetic Wistar rats (type 1 diabetes) induced by STZ, which was associated with the activation of protein kinase C alpha (PKCα) and nuclear factor kappa-B (NF-κB) [16]. A similar increase in the expression of hepatic Mdr1b mRNA was found in STZ-induced diabetic rats [17]. The induction of hepatic P-gp protein expression was also observed in STZ/HFD-induced diabetic rats [11]. However, a report showed that in STZ-induced diabetic Sprague-Dawley rats, 5-week diabetes significantly increased Mdr1a (ABCB1a) and decreased Mdr1b mRNA expression, but significantly decreased expressions of both Mdr1a and Mdr1b mRNA were found in 8-week diabetic rats. Immunoblotting demonstrated that 5-week diabetes significantly reduced the expression of P-gp protein in rats, but the decreases were not found in 8-week diabetic rats, indicating that the regulation of P-gp protein occurred at post-transcriptional level under diabetic status [18].
