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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rosiglitazone treatment | Experimental | Rosiglitazone will be given to the subjects. All subjects will be analyzed before and after treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rosiglitazone | Drug | 89 mg BID for 8 weeks, orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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) | 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 | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 8 weeks |
| Hormonal and metabolic changes induced by the intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Knut Mai | Charite, Dpt. of Endocrinology, Diabetes and Nutrition | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charite, Campus Benjamin Franklin | Berlin | 12200 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21741058 | Derived | Mai K, Andres J, Bobbert T, Assmann A, Biedasek K, Diederich S, Graham I, Larson TR, Pfeiffer AF, Spranger J. Rosiglitazone increases fatty acid Delta9-desaturation and decreases elongase activity index in human skeletal muscle in vivo. Metabolism. 2012 Jan;61(1):108-16. doi: 10.1016/j.metabol.2011.05.018. Epub 2011 Jul 7. |
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| ID | Term |
|---|---|
| D024821 | Metabolic Syndrome |
| D018149 | Glucose Intolerance |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077154 | Rosiglitazone |
| ID | Term |
|---|---|
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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Whole body as well as tissue specific (skeletal muscle and different adipose tissue compartment) changes in hormonal circuits and metabolism will be analyzed |
| 3 months |
| changes of FGF-21 induced by the intervention | FGF-21 (ng/ml) will be assessed in plasma samples | 8 weeks |
| changes of free fatty acids (FFA) induced by the intervention | FFA (mmol/l) will be assessed in plasma samples | 8 weeks |
| changes of myocellular SCD1 expression induced by the intervention | myocellular SCD1 mRNA expression will be assessed | 8 weeks |
| changes of myocellular long chain fatty acids (LC-FA) expression induced by the intervention | myocellular LC-FA mRNA expression will be assessed | 8 weeks |
| D006943 | Hyperglycemia |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |