Drug-metabolizing enzyme and transporter expression in a mouse model of diabetes and obesity

Molecular Pharmaceutics
Qiuqiong ChengAngela L Slitt

Abstract

Obesity and type II diabetes pose a serious human health risk. Obese or diabetic patients usually take prescription drugs that require hepatic and renal metabolism and transport, and these patients sometimes display different pharmacokinetics of these drugs. Therefore, mRNA and protein expression of drug-metabolizing enzymes (DMEs) and transporters was measured in livers and kidneys of adult wild-type and ob/ob mice, which model obesity and diabetes. mRNA expression of numerous DMEs increased by at least 2-fold in livers of male ob/ob mice, including Cyp4a14, Cyp2b10, NAD(P)H:quinone oxidoreductase 1 (Nqo1), and sulfotransferase 2a1/2. In general, expression of uptake transporters was decreased in livers of ob/ob mice, namely organic anion-transporting polypeptides (Oatps) and sodium/taurocholate cotransporting polypeptide (Ntcp). In particular, Oatp1a1 mRNA and protein expression in livers of ob/ob mice was diminished to <5% and <15% of that in wild-types, respectively. Generally, the mRNA and protein expression of efflux transporters multidrug resistance-associated proteins (Mrps) was increased in livers of ob/ob mice, particularly with Mrp4 expression being elevated by at least 6-fold and Mrp2 expression at least 3-fold in l...Continue Reading

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