PII-100

N. Hohmann, A. Maus, A. Carls, A. Blank, W. E. Haefeli, G. Mikus; Department of Clinical Pharmacology, Heidelberg, Germany

BACKGROUND: Pregnane X Receptor (PXR) is implicated in glucose metabolism through transcriptional control of enzymes limiting the rate of gluconeogenesis. Glucose utilization of volunteers treated with the PXR agonist rifampin resembles pre-diabetes and a contributing role of PXR modulators to the diabetes epidemic was suggested. Effects of St. John’s wort (SJW), a PXR inducer, on human glucose metabolism are unknown.
METHODS: We assessed the metabolic effects of SJW alone and in combination with rifampin in 12 healthy volunteers. An oral glucose tolerance test was performed before and upon completion of the 14-day therapy with 1800 mg SJW and 7-day therapy with 1800 mg SJW + 600 mg rifampin daily.
RESULTS: Plasma fasting glucose was significantly reduced by 6.2% and glucose AUC by 12.9% (Fig. 1), while β-cell function increased by 38%. These effects were reversed by rifampin co-administration.
CONCLUSION: While rifampin impairs glucose metabolism SJW treatment lowered fasting glucose in healthy volunteers to a similar extent as metformin. SJW also improved glucose metabolism in streptozotocin-induced diabetic rats therefore SJW effects on glucose levels of type 2 diabetics should be investigated. Differential modulation of gene expression by PXR agonists might explain opposite clinical effects, but remains to be elucidated.
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