title: Pregnane X receptor (PXR)--a contributor to the diabetes epidemic?
abstract: Pregnane X receptor (PXR), a ligand-activated nuclear receptor, was originally identified as a regulator of drug and bile acid metabolism. Studies in experimental animals and humans within the last decade have revealed PXR as a regulator of energy metabolism repressing gluconeogenesis and hepatic lipid oxidation. The most recent in vivo studies demonstrate that PXR activation has a detrimental role in the regulation of glucose metabolism. The prevalence of many PXR agonists in low concentrations in our environments as well as the PXR-activating properties of numerous commonly used medications and herbal remedies may have unanticipated health effects. It could be speculated that, due to its dual role as a xenosensor and a regulator of energy metabolism, PXR, in concert with a mixture of PXR agonists in the environment, contributes to the present-day type 2 diabetes epidemic. With this hypothesis in mind, we review the current literature on PXR as a regulator of glucose and hepatic lipid metabolism and the association of exposure to PXR agonists with diabetes susceptibility.
authors.forename: Janne
authors.initials: J
authors.lastname: Hukkanen
authors.forename: Jukka
authors.initials: J
authors.lastname: Hakkola
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
mesh_terms: D000924:Anticholesteremic Agents / Q000009:adverse effects; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects; D050356:Lipid Metabolism / Q000502:physiology; D016273:Occupational Exposure / Q000009:adverse effects; D028321:Plant Preparations / Q000009:adverse effects; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000924:Anticholesteremic Agents; D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D028321:Plant Preparations; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid