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Rosiglitazone decreases 11β‐hydroxysteroid dehydrogenase type 1 in subcutaneous adipose tissue
Author(s) -
Mai Knut,
Andres Janin,
Bobbert Thomas,
MaserGluth Christiane,
Möhlig Matthias,
Bähr Volker,
Pfeiffer Andreas F. H.,
Spranger Joachim,
Diederich Sven
Publication year - 2007
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2007.02903.x
Subject(s) - medicine , endocrinology , rosiglitazone , 11β hydroxysteroid dehydrogenase type 1 , insulin resistance , cortisone , adipose tissue , glucocorticoid , postprandial , insulin , chemistry , dehydrogenase , enzyme , biochemistry
Summary Objective The peroxisome proliferator‐activated receptor‐γ (PPARγ) agonist rosiglitazone increases insulin sensitivity, which, in animal models, is comparable to the effect of a reduction in 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) activity. We therefore investigated whether rosiglitazone‐induced insulin sensitivity is associated with changes in 11β‐HSD1 activity in different tissues. Methods An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp were performed in seven male volunteers [age 59·3 ± 3·0 years, body mass index (BMI) 29·3 ± 4·1 kg/m 2 ] with impaired glucose tolerance before and after 8 weeks of rosiglitazone treatment. To assess hepatic 11β‐HSD1 activity, serum cortisol levels were measured after oral administration of cortisone acetate. 11β‐HSD1 activity and mRNA expression were assessed in abdominal subcutaneous fat biopsies. Total‐body 11β‐HSD activities were estimated by calculating the urinary ratios of glucocorticoid metabolites. Results As expected, rosiglitazone improved insulin resistance and postprandial hyperglycaemia. In parallel, 11β‐HSD1 mRNA expression [100 ± 0% (reference) vs. 68·5 ± 9·3%, P < 0·01] and activity [0·18 ± 0·02 vs. 0·13 ± 0·02 pmol/min/mg, P < 0·05] decreased in abdominal subcutaneous fat, while an increase in hepatic 11β‐HSD1 activity was detected [the area under the curve (AUC) for the cortisol/cortisone ratio was 1319 ± 76 vs. 955 ± 59; P < 0·05]. No changes in BMI, waist‐to‐hip ratio (WHR) and whole‐body 11β‐HSD1 activity were found. Conclusions Part of the beneficial effects of rosiglitazone may be mediated by a reduction in the 11β‐HSD1 mRNA expression and activity in subcutaneous abdominal fat.