Endocrine Abstracts

Current dogma suggests that glucocorticoids (GCs) cause insulin resistance in all tissues. Whilst it is clear that they cause global, whole body insulin resistance, we have challenged the concept that the actions of GCs are the same in all tissues. Using a variety of human cell-based models, we have shown that in contrast to their actions in skeletal muscle and liver, GCs cause insulin sensitization in human adipose tissue, enhancing insulin-stimulated PKB/akt phosphorylation,...

Synthetic glucocorticoids (GCs) including dexamethasone (Dex) are potent anti-inflammatory drugs. However, long-term use of GCs results in deleterious side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The nuclear hormone receptors LXRα and LXRβ are known for their important roles in modulating whole-body cholesterol homeostasis. Recently, we have shown that liver X receptor β (LXRβ) knockout mice are protected against Dex-induced ...

Excessive glucocorticoid action is detrimental to metabolic health. The last 15 years has seen the emergence of enzymatic intra-cellular glucocorticoid reactivation, driven by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), as a key mechanism contributing to glucocorticoid action. In most contexts, high intracellular glucocorticoid regeneration results in adverse metabolic effects. Inhibition or gene knockout of 11β-HSD1 is metabolically protectiv...