Renal drug transporter expression in pregnant mice with type 1 diabetes

Abstract

Sex hormones and metabolic changes (such as obesity and hyperglycemia) can alter renal transporter expression in rodents. The purpose of this study was to investigate renal transporter expression in response to pregnancy and type 1 diabetes. Female mice were treated with vehicle or the diabetogenic drug, streptozotocin (STZ) 2 weeks prior to mating. Renal transporter mRNA and protein expression were evaluated in vehicle‐ and STZ‐treated pregnant and virgin mice. The majority of renal transporters were unaffected by pregnancy in vehicle‐treated mice, with only modest 40–80% increases in Mrp3, Oatp2b1, Pept1, and Cnt1 mRNA. In contrast, renal transporters were markedly changed in STZ‐treated virgin mice with decreased Oat2, 5, and Mrp3 mRNA and elevated Oatp2b1, 4c1, Mrp2, 4, 5, and Pept1 mRNA. In combination, STZ treatment and pregnancy downregulated Oatp4c1, Mdr1b, and Mrp3 mRNA. Transcriptional profiling suggests Hnf1α, Nrf2, PXR, AhR, and PPARα may be involved in regulating renal transporter expression. In conclusion, renal drug transport pathways are altered by hormone changes that occur during pregnancy and diabetes. Supported by ES‐007148, ES‐005022, DK‐080774, ES‐020522.