Coffee inhibits the reactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1: A glucocorticoid connection in the anti-diabetic action of coffee?

Recent epidemiological studies demonstrated a beneficial effect of coffee consumption for the prevention of type 2 diabetes, however, the underlying mechanisms remained unknown. We demonstrate that coffee extract, corresponding to an Italian Espresso, inhibits recombinant and endogenous 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. The inhibitory component is heat-stable with considerable polarity. Coffee extract blocked 11β-HSD1-dependent cortisol formation, prevented the subsequent nuclear translocation of the glucocorticoid receptor and abolished glucocorticoid-induced expression of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. We suggest that at least part of the anti-diabetic effects of coffee consumption is due to inhibition of 11β-HSD1-dependent glucocorticoid reactivation.