Journal article

Evidence for transcript-specific epigenetic regulation of glucocorticoid-stimulated skeletal muscle 11 beta-hydroxysteroid dehydrogenase-1 activity in type 2 diabetes

Warrick J Inder, Varuni R Obeyesekere, Christina Jang, Richard Saffery



BACKGROUND: The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) converts inactive cortisone into active cortisol in insulin target tissues. In people with type 2 diabetes, skeletal muscle (SkM) 11βHSD1 is upregulated by the potent glucocorticoid dexamethasone. The HSD11B1 gene has two promoters designated P1 and P2. CCAAT/enhancer-binding protein beta (C/EBPβ) is known to regulate expression of 11βHSD1 via the P2 promoter. In this study, we investigated the potential role of altered DNA methylation of the P1 and P2 promoters in the observed dexamethasone-induced upregulation of SkM 11βHSD1 oxoreductase activity in human diabetic subjects. SkM biopsies from 15 people with type 2 diab..

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Funding Acknowledgements

Dr Christina Jang was awarded the Novartis Oncology Endocrinology Fellowship from the Royal Australasian College of Physicians in 2009. This study was funded in part by a grant from the Diabetes Australia Research Trust (DART). Special thanks to Nick Wong, Boris Novakovic and HK Ng for their help with Sequenom MassARRAY Epityping.