Publications by authors named "E Wagenaar"

Article Synopsis
  • - Carboxylesterase 2 (CES2) is primarily found in the liver and intestine, playing a significant role in metabolizing various compounds, influencing drug effectiveness, and affecting lipid and glucose metabolism.
  • - The study involved creating knockout mice lacking CES2 genes and transgenic mice with human CES2 to assess the effects of CES2 on drug metabolism and metabolic health.
  • - Findings revealed that while the absence of CES2 led to fatty liver and metabolic issues, introducing human CES2, especially in the intestine, improved these conditions and could potentially address metabolic syndrome challenges.
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Article Synopsis
  • Transmembrane drug transporters significantly influence how drugs are processed in the body, affecting their effectiveness and safety.
  • Researchers created a new mouse model (Bab12) lacking certain drug transporters to study their impacts on drug levels and interactions.
  • Findings indicated varying effects of transporter deficiencies on different drugs, highlighting the importance of transporter interplay in drug development and the potential for using the Bab12 model to enhance pharmacological studies.
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Mammalian carboxylesterase 1 enzymes can hydrolyze many xenobiotic chemicals and endogenous lipids. We here identified and characterized a mouse strain (FVB/NKI) in which three of the eight Ces1 genes were spontaneously deleted, removing Ces1c and Ces1e partly, and Ces1d entirely. We studied the impact of this Ces1c/d/e deficiency on drug and lipid metabolism and homeostasis.

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Organic anion transporting polypeptide 2B1 (OATP2B1/SLCO2B1) facilitates uptake transport of structurally diverse endogenous and exogenous compounds. To investigate the roles of OATP2B1 in physiology and pharmacology, we established and characterized Oatp2b1 knockout (single Slco2b1 and combination Slco1a/1b/2b1) and humanized hepatic and intestinal OATP2B1 transgenic mouse models. While viable and fertile, these strains exhibited a modestly increased body weight.

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The mammalian carboxylesterase 1 (Ces1/CES1) family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous lipids. To investigate the pharmacological and physiological roles of Ces1/CES1, we generated cluster knockout ( ) mice, and a hepatic human CES1 transgenic model in the background (TgCES1). mice displayed profoundly decreased conversion of the anticancer prodrug irinotecan to SN-38 in plasma and tissues.

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