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FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance
Metabolism, clinical and experimental, 2014-09, Vol.63 (9), p.1198-1208
2014

Details

Autor(en) / Beteiligte
Titel
FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance
Ist Teil von
  • Metabolism, clinical and experimental, 2014-09, Vol.63 (9), p.1198-1208
Ort / Verlag
New York, NY: Elsevier Inc
Erscheinungsjahr
2014
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • Abstract Objective To study effects of dexamethasone on gene expression in human adipose tissue aiming to identify potential novel mechanisms for glucocorticoid-induced insulin resistance. Materials/methods Subcutaneous and omental adipose tissue, obtained from non-diabetic donors (10 M/15 F; age: 28–60 years; BMI: 20.7–30.6 kg/m2 ), was incubated with or without dexamethasone (0.003–3 μmol/L) for 24 h. Gene expression was assessed by microarray and real time-PCR and protein expression by immunoblotting. Results FKBP5 (FK506-binding protein 5) and CNR1 (cannabinoid receptor 1) were the most responsive genes to dexamethasone in both subcutaneous and omental adipose tissue (~ 7-fold). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots. The gene product, FKBP51 protein, was 10-fold higher in the omental than in the subcutaneous depot, whereas the mRNA levels were similar. Higher FKBP5 gene expression in omental adipose tissue was associated with reduced insulin effects on glucose uptake in both depots. Furthermore, FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter and negatively with plasma HDL-cholesterol. FKBP5 SNPs were found to be associated with type 2 diabetes and diabetes-related phenotypes in large population-based samples. Conclusions Dexamethasone exposure promotes expression of FKBP5 in adipose tissue, a gene that may be implicated in glucocorticoid-induced insulin resistance.
Sprache
Englisch
Identifikatoren
ISSN: 0026-0495, 1532-8600
eISSN: 1532-8600
DOI: 10.1016/j.metabol.2014.05.015
Titel-ID: cdi_swepub_primary_oai_gup_ub_gu_se_203115
Format
–
Schlagworte
Adipose tissue, Adult, Biological and medical sciences, Biological Transport - drug effects, Cells, Cultured, Dexamethasone - pharmacology, Endocrinology & Metabolism, Endocrinology and Diabetes, Endokrinologi och diabetes, Endothelium, Vascular - cytology, Endothelium, Vascular - drug effects, Endothelium, Vascular - metabolism, Feeding. Feeding behavior, FKBP5, Fundamental and applied biological sciences. Psychology, Gene expression, Gene Expression Regulation - drug effects, Glucocorticoids, Glucocorticoids - pharmacology, Glucose - metabolism, Humans, Insulin - blood, Insulin - pharmacology, Insulin Resistance, Intra-Abdominal Fat - blood supply, Intra-Abdominal Fat - cytology, Intra-Abdominal Fat - drug effects, Intra-Abdominal Fat - metabolism, Male, Middle Aged, Osmolar Concentration, Receptor, Cannabinoid, CB1 - agonists, Receptor, Cannabinoid, CB1 - genetics, Receptor, Cannabinoid, CB1 - metabolism, RNA, Messenger - metabolism, Stromal Cells - cytology, Stromal Cells - drug effects, Stromal Cells - metabolism, Subcutaneous Fat, Abdominal - blood supply, Subcutaneous Fat, Abdominal - cytology, Subcutaneous Fat, Abdominal - drug effects, Subcutaneous Fat, Abdominal - metabolism, Tacrolimus Binding Proteins - chemistry, Tacrolimus Binding Proteins - genetics, Tacrolimus Binding Proteins - metabolism, Vertebrates: anatomy and physiology, studies on body, several organs or systems

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