title: Renal efflux transporter expression in pregnant mice with Type I diabetes.
abstract: Prior research suggests that sex hormones and metabolic changes, such as obesity and hyperglycemia, can alter renal transporter expression in rodents. The purpose of this study was to characterize the expression of kidney efflux transporters and regulatory transcription factors in response to Type I diabetes and pregnancy. Female C57BL/6 mice were treated with multiple low doses of streptozotocin (STZ) to induce hyperglycemia and then mated with normoglycemic male mice. Transporter mRNA and protein expression were quantified in kidneys from vehicle- and STZ-treated non-pregnant and pregnant mice on gestation day 14. Pregnancy decreased the expression of Mdr1b, Mrp4, and 5 proteins and increased the mRNA and protein expression of Mrp3 by 50-60%. STZ treatment elevated Mrp1, 2, 4, and 5 and reduced Mrp3, 6, and Mdr1b mRNA and/or protein in non-pregnant mice. Pregnancy had little effect on STZ-mediated changes in renal efflux transporter expression. Transcriptional profiles of Hnf1α, PXR, AhR, and Nrf2 were altered in patterns similar to some efflux transporters suggesting potential involvement in their regulation. Taken together, these results suggest that renal drug efflux transporters and regulatory signaling pathways are altered by endocrine and metabolic changes that occur during pregnancy and Type I diabetes.
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Rd, Piscataway, NJ 08854, USA.
authors.forename: Lindsay L
authors.initials: LL
authors.lastname: Yacovino
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Aleksunes
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D000090702:Constitutive Androstane Receptor; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000187:drug effects; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000096:biosynthesis; D010179:Pancreas / Q000473:pathology; D011247:Pregnancy; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D011987:Receptors, Steroid / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D001786:Blood Glucose; D002352:Carrier Proteins; D000090702:Constitutive Androstane Receptor; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D051267:NF-E2-Related Factor 2; D047493:PPAR alpha; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid