Pregnancy represses induction of hepatobiliary efflux transporters in diabetic mice

Abstract

Efflux transporters are plasma membrane proteins responsible for excreting chemicals and toxicants from the cell. In the liver, efflux transporters including the multidrug resistance‐associated proteins (Mrps) are markedly induced in mice with diabetes. In contrast, other conditions such as pregnancy decrease hepatic Mrp levels. The purpose of the present study was to quantify the mRNA expression of hepatobiliary efflux transporters in pregnant, diabetic mice. Female mice were treated with vehicle or streptozotocin (STZ). Once STZ‐treated mice exhibited elevated glucose levels, they were mated with male mice. mRNA expression was quantified in livers of nonpregnant and pregnant female mice with normal or elevated glucose levels. Livers from nonpregnant, diabetic mice exhibited up‐regulation of Mrp1, 2, 4, 5 and breast cancer resistance protein (Bcrp) mRNA that was attenuated in pregnant, diabetic mice. Mrp3 mRNA was similarly induced in livers of nonpregnant and pregnant diabetic mice. Mrp6 mRNA was decreased by pregnancy, regardless of glucose level. Collectively, these data suggest that pregnancy represses expression of efflux transporters in livers of diabetic mice. Additional studies are necessary to elucidate the transcriptional mechanisms underlying the opposing regulation of hepatobiliary transporters in response to diabetes and pregnancy. Supported by NIH ES016042, ES005022, DK080774.