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Pregnane X Receptor Agonists Impair Postprandial Glucose Tolerance
Author(s) -
Rysä J,
Buler M,
Savolainen M J,
Ruskoaho H,
Hakkola J,
Hukkanen J
Publication year - 2013
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2013.48
Subject(s) - postprandial , pregnane x receptor , endocrinology , medicine , agonist , glucose homeostasis , insulin , glucose tolerance test , insulin resistance , blood sugar regulation , crossover study , glut2 , glucose transporter , partial agonist , chemistry , pharmacology , placebo , receptor , nuclear receptor , biochemistry , alternative medicine , pathology , transcription factor , gene
We conducted a randomized, open, placebo‐controlled crossover trial to investigate the effects of the pregnane X receptor (PXR) agonist rifampin on an oral glucose tolerance test (OGTT) in 12 healthy volunteers. The subjects were administered 600 mg rifampin or placebo once daily for 7 days, and OGTT was performed on the eighth day. The mean incremental glucose and insulin areas under the plasma concentration–time curves (AUC incr ) increased by 192% ( P = 0.008) and 45% ( P = 0.031), respectively. The fasting glucose, insulin, and C‐peptide, and the homeostasis model assessment for insulin resistance, were not affected. The glucose AUC incr during OGTT was significantly increased in rats after 4‐day treatment with pregnenolone 16α‐carbonitrile (PCN), an agonist of the rat PXR. The hepatic level of glucose transporter 2 (Glut2) mRNA was downregulated by PCN. In conclusion, both human and rat PXR agonists elicited postprandial hyperglycemia, suggesting a detrimental role of PXR activation on glucose tolerance. Clinical Pharmacology & Therapeutics (2013); 93 6, 556–563. doi: 10.1038/clpt.2013.48