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DOI: 10.1055/s-2006-933079
Rosiglitazone lead to an decrease in 11ß-HSD1 activity in subcutaneous adipose tissue
Introduction: The PPARχ agonist rosiglitazone (R) increases insulin sensitivity, which is comparable to the effects of a reduction in 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activity in animal models. We therefore aimed to investigate whether Rosiglitazone-induced insulin sensitivity is associated with a decrease in 11ß-HSD1 activity in different tissues.
Study design: 7 male volunteers with impaired glucose tolerance were studied (59.3±7.9 years, BMI 29.3±4.1kg/m2). Before and after 12 weeks of rosiglitazone treatment (2×8mg/d) an oral glucose tolerance test (ogtt) and an euglycemic hyperinsulinemic clamp were performed. To assess hepatic 11ß-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate. Fat biopsies were performed to assess the 11ß-HSD1 activity in abdominal subcutaneous fat by a radioactive enzyme activity test. In addition, total body 11ß-HSD activities were determined in vivo by calculating the urinary ratios of glucocorticoid metabolites.
Results: As expected rosiglitazone improved insulin resistance (M-value R vs. baseline: 5.73±0.45 vs. 3.89±0.68mg/kg/min; p<0.05) and postprandial hyperglycemia (2h-glucose R vs. baseline: 139.7±10.0mg/dl vs. 168.7±7.6mg/dl; p<0.05). In parallel 11ß-HSD1 activity decreased in abdominal subcutaneous fat (0.18±0.02 vs. 0.13±0.02 pmol/min/mg; p<0.05), while an increase in hepatic 11ß-HSD1 activity, as measured by an increase in cortisol-cortison-ratio, was detected. No changes in BMI, WHR and whole-body-11ß-HSD1 activity, as estimated by urinary ratios of glucocorticoid metabolites, were found.
Summary: We conclude that parts of the beneficial effects of rosiglitazone may be mediated by reduction of the 11ß-HSD1-activity in subcutaneous abdominal fat.