Abstract
Drug efflux transporters in the placenta can significantly influence the materno-fetal transfer of a diverse array of drugs and other xenobiotics. To determine if clinically important drug efflux transporter expression is altered in pregnancies complicated by gestational diabetes mellitus (GDM-I) or type 1 diabetes mellitus (T1DM-I), we compared the expression of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 2 (MRP2) and the breast cancer resistance protein (BCRP) via western blotting and quantitative real-time polymerase chain reaction in samples obtained from insulin-managed diabetic pregnancies to healthy term-matched controls. At the level of mRNA, we found significantly increased expression of MDR1 in the GDM-I group compared to both the T1DM-I (p<0.01) and control groups (p<0.05). Significant changes in the placental protein expression of MDR1, MRP2, and BCRP were not detected (p>0.05). Interestingly, there was a significant, positive correlation observed between plasma hemoglobin A1c levels (a retrospective marker of glycemic control) and both BCRP protein expression (r = 0.45, p<0.05) and BCRP mRNA expression (r = 0.58, p<0.01) in the insulin-managed DM groups. Collectively, the data suggest that the expression of placental efflux transporters is not altered in pregnancies complicated by diabetes when hyperglycemia is managed; however, given the relationship between BCRP expression and plasma hemoglobin A1c levels it is plausible that their expression could change in poorly managed diabetes.
Highlights
Over 220 million people worldwide are diagnosed with diabetes and rising prevalence is reported in most surveyed populations [1,2]
Multidrug resistance protein (MDR) 1 (P-glycoprotein; Gene: ABCB1), multidrug resistanceassociated protein 2 (MRP2; Gene: ABCC2) and the breast cancer resistance protein (BCRP; Gene: ABCG2) are abundantly expressed ATP-binding cassette (ABC) drug efflux transporters found in the apical localization of the placental syncytiotrophoblast layer (Fig. 1)
We have previously demonstrated that placental multidrug resistance protein 1 (MDR1), MRP2 and BCRP mRNA expression is elevated in rat dams with streptozotocin-induced gestational diabetes mellitus (GDM) but nearly normal in rat dams with streptozotocin-induced GDM whose blood glucose was normalized following insulin treatment
Summary
Over 220 million people worldwide are diagnosed with diabetes and rising prevalence is reported in most surveyed populations [1,2]. These profound results and the increasing prevalence of diabetes mellitus in pregnancy prompted us to study the impact of GDM and T1DM on placental transporter expression.
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