Endocrine Abstracts

The metabolic syndrome, which encompasses features of obesity, insulin resistance, dyslipidaemia and hypertension, has been associated with excessive glucocorticoid (GC) exposure. The pancreas is a target of the adverse affects of GC action, resulting in β-cell damage and reduced glucose-stimulated insulin secretion (GSIS). 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyses the in vivo conversion of inactive to active glucocorticoids (cortisone E/11-de...

Dehydroepiandrosterone (DHEA) and its sulphate ester DHEAS, have been shown to oppose the effects of glucocorticoids in vivo, thus producing beneficial effects on insulin sensitivity in rodent models of diabetes and obesity as well as in hypoadrenal patients. Glucocorticoids play a key role in regulating fat metabolism and distribution and are reactivated locally by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) oxoreductase activity, which increases with ...

Glucocorticoids (GC) have potent actions upon human adipose tissue, promoting adipocyte differentiation, inhibiting preadipocyte proliferation and inducing lipolysis to generate free fatty acids (FFA) and glycerol through a putative action upon hormone sensitive lipase (HSL). FFA have been strongly implicated in the pathogenesis of insulin resistance, yet the molecular mechanisms that cause GC induced lipolysis are not clear. Recently, several novel lipases have been identifie...

Glucocorticoid (GC) excess is characterized by central obesity, insulin resistance and in some cases, type 2 diabetes mellitus. Whilst it is accepted that GCs cause insulin resistance, both insulin and GCs act synergistically to promote adipocyte differentiation. We have previously shown that GCs cause tissue specific changes in insulin sensitivity, enhancing insulin signalling in human adipose tissue in contrast to muscle.TRB3, a mammalian homolog of <i...

Human studies have suggested that local glucocorticoid (GC) generation within osteoblasts plays a critical role in bone loss seen during aging, in response to inflammation and treatment with GCs. Human osteoblasts express the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that converts inactive GCs (cortisone, dehydrocorticosterone, prednisone) to their active counterparts (cortisol, corticosterone, prednisolone). Enzyme expression increases with age, in r...

Hyponatraemia is the commonest electrolyte abnormality in hospitalised patients. It is often seen in patients with complex medical problems and in the critically ill. We determined the outcome for patients identified to have hyponatraemia over a one month period.Methods: We reviewed all in-patients with severe hyponatraemia, defined as serum sodium <125 mmol/l (135–146) at Hope Hospital during April 2005. Patients were identified retrospectively...

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 high dose short Synacthen (corticotropin) test (SST) is widely used to investigate suspected secondary adrenal insufficiency but concern remains about falsely reassuring results with potentially serious clinical consequences.In order to evaluate the long-term safety of the SST, we retrospectively evaluated the clinical outcome in 178 patients who achieved 30-minute cortisol values in the lowest 15th percentile of normal healthy responses. This subgro...

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...