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Licensed Unlicensed Requires Authentication Published by De Gruyter October 29, 2013

Pregnane X receptor (PXR) – a contributor to the diabetes epidemic?

  • Janne Hukkanen EMAIL logo , Jukka Hakkola and Jaana Rysä

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.


Corresponding author: Janne Hukkanen, Department of Internal Medicine, Oulu University Hospital, P.O. Box 20, FI-90029 Oulu, Finland, E-mail:

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Received: 2013-7-1
Accepted: 2013-9-25
Published Online: 2013-10-29
Published in Print: 2014-02-01

©2014 by Walter de Gruyter Berlin Boston

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