Searchable abstracts of presentations at key conferences in endocrinology

ea0011p307 | Diabetes, metabolism and cardiovascular | ECE2006

Altered cholesterol and bile acid homeostasis in the hexose-6-phosphate dehydrogenase (H6PDH) knockout mouse

Hewitt KN , Bujalska IJ , Lavery GG , Stewart PM , Walker EA

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 ...

ea0011p406 | Diabetes, metabolism and cardiovascular | ECE2006

Dehydroepiandrosterone inhibits differentiation, proliferation and 11β-hydroxysteroid dehydrogenase type 1 activity in human preadipocytes

McNelis J , Bujalska IJ , Stewart PM , Arlt W

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...

ea0011p745 | Steroids | ECE2006

Tissue specific regulation of insulin signalling: a mechanism of glucocorticoid induced obesity?

Gathercole LL , Bujalska IJ , Stewart PM , Tomlinson JW

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...

ea0011p757 | Steroids | ECE2006

11beta-hydroxysteroid dehydrogenase is an early and essential marker of human adipogenesis

Bujalska IJ , Gatherocole LL , Tomlinson JW , Darimont C , Stewart PM

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...

ea0019oc5 | Young Endocrinologist prize session | SFEBES2009

Selective inhibition of 11β-hydroxysteroid dehydrogenase type 1 improves insulin sensitivity in skeletal muscle through modulation of IRS1 serine phosphorylation

Morgan SA , Gathercole LL , Lavery GG , Sherlock M , Bujalska IJ , Sethi JK , Hegyi K , Stewart PM , Smith DM , Tomlinson JW

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...