Coffee inhibits the reactivation of glucocorticoids by 11beta-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 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity. The inhibitory component is heat-stable with considerable polarity. Coffee extract blocked 11beta-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 11beta-HSD1-dependent glucocorticoid reactivation.
Atanasov
Atanas G
AG
Division of Nephrology and Hypertension, Department of Clinical Research, University of Berne, Freiburgstrasse 15, 3010 Berne, Switzerland.
Dzyakanchuk
Anna A
AA
Schweizer
Roberto A S
RA
Nashev
Lyubomir G
LG
Maurer
Evelyne M
EM
Odermatt
Alex
A
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002262:Carboxy-Lyases / Q000096:biosynthesis; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D040503:Coffea / Q000737:chemistry; D003069:Coffee / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000517:prevention & control; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism
D003069:Coffee; D005938:Glucocorticoids; D010936:Plant Extracts; D011965:Receptors, Glucocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D002262:Carboxy-Lyases; D006854:Hydrocortisone