Environmental xenosensor PXR as a disease mechanism and therapeutic target in metabolic diseases - Jukka Hakkola and Janne Hukkanen
Pregnane X receptor (PXR) is a nuclear receptor with a wide ligand acceptance, including environmental contaminants, herbal remedies, as well as clinically used drugs. PXR was originally discovered as a regulator of drug metabolizing enzymes, but the recent studies have established a role in the regulation of hepatic glucose and lipid metabolism. In fact, PXR activation may significantly contribute to the development of metabolic diseases.
We utilize translational approach to reveal the role of PXR in metabolic diseases and apply methods from basic molecular biology to in vivo animal experiments and clinical human studies. Our group provided the first evidence that PXR activation impairs glucose tolerance in humans and in rodents. In our future research we aim to characterize the role of PXR as a disease mechanism and as a potential therapeutic target in closely related metabolic diseases, such as type 2 diabetes, hypertension, NAFLD and metabolic syndrome.
Hassani-Nezhad-Gashti F., Rysä J., Kummu O., Näpäkangas J., Buler M., Karpale M., Hukkanen J., Hakkola J., Activation of nuclear receptor PXR impairs glucose tolerance and dysregulates GLUT2 expression and subcellular localization in liver. Biochem. Pharmacol. (2018), 148, 253-264.
Rysä J., Buler M., Savolainen M.J., Ruskoaho H., Hakkola J., Hukkanen J., Pregnane X receptor agonists impair postprandial glucose tolerance. Clin. Pharmacol. Ther. (2013), 93, 556-563.
Hakkola J., Rysä J., Hukkanen J., Regulation of hepatic energy metabolism by the nuclear receptor PXR. Biochim. Biophys. Acta, Gene Regul. Mech. (2016), 1859, 1072-1082.