Journal
METABOLISM-CLINICAL AND EXPERIMENTAL
Volume 63, Issue 9, Pages 1198-1208Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2014.05.015
Keywords
Glucocorticoids; Adipose tissue; FKBP5; Gene expression; Insulin resistance
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Funding
- AstraZeneca RD
- University of Gothenburg/Sahlgrenska University Hospital [LUA/ALF ALFGBG-11379]
- Portuguese Foundation for Science and Technology [SFRH/BD/41044/2007, PTDC/SAU-OSM/104124/2008]
- Regional FoU-support Vastra Gotalandsregionen [VGFOUREG-12052]
- Swedish Heart and Lung Foundation project [20100648]
- Research Fund of the Swedish Diabetes Association
- Fundação para a Ciência e a Tecnologia [SFRH/BD/41044/2007] Funding Source: FCT
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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 nondiabetic donors (10 M/15 F; age: 28-60 years; BMI: 20.7-30.6 kg/m(2)), was incubated with or without dexamethasone (0.003-3 mu mol/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 (similar to 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. (C) 2014 Elsevier Inc. All rights reserved.
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