Endocrine Abstracts

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulphate ester, DHEAS have been shown to oppose the effects of glucocorticoids, thereby producing beneficial effects on insulin sensitivity in rodent models of diabetes and obesity and in hypoadrenal patients. Glucocorticoids, key regulators of adipose differentiation and insulin sensitivity, are reactivated locally by 11β-hydroxysteroid dehydrogenase type (11β-HSD1) oxoreductase activity, which increases with...

Type 2 diabetes manifests when pancreatic β-cells secrete inadequate insulin in response to elevated glucose. A known culprit in metabolic diseases is excessive exposure to glucocorticoids (GCs). GCs increase hepatic gluconeogenesis, decrease insulin sensitivity in skeletal muscle and adipose tissue and suppress the development of β-cells. In rodents, inactive GC 11-dehydrocorticosterone (A) is converted to active corticosterone (B) by the enzyme 11β-hydroxyster...

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...

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...

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 excess, Cushing's syndrome, is a recognised cause of insulin resistance and in some cases diabetes mellitus. In addition, patients develop reversible central obesity. However, the exact mechanisms that underpin the development of glucocorticoid mediated insulin resistance and central obesity are not known. We have hypothesized that at a cellular level, the tissue specific generation of cortisol from inactive cortisone through the action of 11beta-hydroxysteroid ...