Evidence for transcript-specific epigeneticregulation of glucocorticoid-stimulated skeletalmuscle 11beta-hydroxysteroid dehydrogenase-1 activityin type 2 diabetes

Dexamethasone treatment resulted in a significant increase in 11betaHSD1 mRNA levels (P = 0.003), oxoreductase activity (P = 0.017) and C/EBPbeta mRNA (P = 0.015), and increased expression of both the P1 (P = 0.008) and P2 (P = 0.016) promoter regions . The distal P1 promoter region showed a significant reduction in methylation following dexamethasone (P = 0.026). There was a significant negative correlation between the change in methylation at this site and the increment in 11betaHSD1 oxoreductase activity (r = 0.62, P = 0.014).Our findings of reduced methylation in the HSD11B1 P1 promoter in association with increased 11betaHSD1 oxoreductase activity implicate complex multi-promoter epigenetic mechanisms in the regulation of 11betaHSD1 levels in SkM.