The purpose of this study is to determine whether the insulin sensitizing effects of rosiglitazone were accompanied by changes in 11ß-HSD1 expression and activity in different tissues. Furthermore the metabolic and hormonal effects of PPAR gamma stimulation by rosiglitazone will be analysed in several tissues.
The PPARgamma agonist rosiglitazone (R) increases insulin sensitivity, which is comparable to the effects of a reduction in 11ß-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity in animal models. We therefore aimed to investigate whether rosiglitazone-induced insulin sensitivity is associated with changes in 11β-HSD1 activity in different tissues in subjects suffering from impaired glucose tolerance. Furthermore the metabolic and hormonal effects of PPAR gamma stimulation by rosiglitazone will be analysed in those tissue samples.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
89 mg BID for 8 weeks, orally
Charite, Campus Benjamin Franklin
Berlin, Germany
changes of 11ß-HSD1 expression in adipose tissue and skeletal muscle during 8 weeks of rosiglitazone treatment
11ß-HSD1 expression will be measured in adipose tissue and skeletal muscle
Time frame: 8 weeks
changes of hepatic 11ß-HSD1 activity during 8 weeks of rosiglitazone treatment
11ß-HSD1 activity will be assessed by measuring conversion of cortisone to cortisol (ratio will be calculated)
Time frame: 8 weeks
changes of whole body 11ß-HSD1 activity during 8 weeks of rosiglitazone treatment
whole body 11ß-HSD1 activity will be assessed by measuring the ratio of urinary tetrahydrocortisol (THF) + alpha-tetrahydrocortisol (THF) / tetrahydrocortisone
Time frame: 8 weeks
changes in insulin sensitivity during 8 weeks of rosiglitazone treatment
Measurement of whole body and myocellular insulin sensitivity (mg•kg-1•min-1/(mU•L-1)) before and after treatment
Time frame: 8 weeks
Hormonal and metabolic changes induced by the intervention
Whole body as well as tissue specific (skeletal muscle and different adipose tissue compartment) changes in hormonal circuits and metabolism will be analyzed
Time frame: 3 months
changes of FGF-21 induced by the intervention
FGF-21 (ng/ml) will be assessed in plasma samples
Time frame: 8 weeks
changes of free fatty acids (FFA) induced by the intervention
FFA (mmol/l) will be assessed in plasma samples
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Time frame: 8 weeks
changes of myocellular SCD1 expression induced by the intervention
myocellular SCD1 mRNA expression will be assessed
Time frame: 8 weeks
changes of myocellular long chain fatty acids (LC-FA) expression induced by the intervention
myocellular LC-FA mRNA expression will be assessed
Time frame: 8 weeks