Endocrine Abstracts

In humans, glucocorticoids (GC) are implicated in the pathogenesis of obesity and insulin resistance. GCs are regulated at the prereceptor level by 11beta-hydroxysteroid dehydrogenases (11β-HSD). 11β-HSD type 1 (11β-HSD1) predominantly displays oxo-reductase activity, converting cortisone in man, 11-dehydrocorticosterone in rodents, to cortisol and corticosterone respectively – a reaction requiring the cofactor NADPH. The generation of a hexose-6-phosphate ...

The adrenal steroid dehydroepiandrosterone (DHEA) has been shown in vivo, to mimic the effects of peroxosome proliferator-activated receptor (PPAR) ligands and oppose those of glucocorticoids, thus producing beneficial effects on insulin sensitivity and adipogenesis in obese and diabetic rodents. Furthermore, DHEA treatment has recently been shown to reduce subcutaneous and visceral fat in humans in vivo. However, the mechanism by which DHEA produces these anti-a...

The pathological effects of glucocorticoids (GC) are exemplified by patients with Cushing’s syndrome who develop central obesity, insulin resistance and in some cases, type 2 diabetes mellitus. It is generally accepted that GC cause insulin resistance, however, both insulin and GC increase adipocyte differentiation. The question therefore arises as to how GC stimulate adipocyte differentiation whilst apparently making adipocytes insulin resistant. We have hypothesized tha...

The prevalence of obesity and its association with many health complications have evoked a high interest in adipose tissue metabolism. In man, glucocorticoid (GC) excess increases fat mass and the risk of developing Metabolic Syndrome. The enzyme responsible for modifying intracellular GC concentrations in adipose tissue is 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The aim of this study was to characterise the novel human preadipocyte cell line (Chub-S7) an...

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite increasing use of GCs as therapeutic agents, the precise molecular mechanisms that underpin GC-induced insulin resistance are unknown. Within skeletal muscle, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to the active GC, cortisol (corticosterone in rodents) and thus amplifies local GC act...