Endocrine Abstracts

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 acute treatment (24 h) with GCs enhances insulin signalling in human adipocytes. We hypothesise that the generation of cortisol from inactive cortisone by 11β-hydroxysteroid dehydrog...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Obesity occurs as a consequence of increased adipocyte size (hypertrophy) and number (differentiation or hyperplasia). Whilst differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, the molecular mechanisms that underpin the differences in adipose tissue biology and the depot specific metabolic risks that th...

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...

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 enzyme 5β-reductase (AKR1D1) catalyses an essential step in bile acid (BA) synthesis, but in addition, controls intra-cellular steroid hormone availability by inactivation. Steroid hormones and BA are regulators of global lipid and carbohydrate metabolism. As disturbances in steroid hormone and BA metabolism have potent effects on metabolic health, we hypothesize that AKR1D1 may play a role in metabolic homeostasis. The role of AKR1D1 in regulating glucose homeostasis...

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). 5β-reductase (AKR1D1) is a liver enzyme that catalyses a fundamental step in bile acid (BA) synthesis. Both BAs and BA intermediates are established as potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial role in NAFLD and HCC. Human liver b...

The 5-reductases are steroid metabolising enzymes that saturate the C4=C5 bond of the steroid A-ring, and their substrates include androgens, glucocorticoids, and bile acids. 5β-reductases (SRD5A1 & SRD5A2) convert testosterone to the more potent androgen 5β-dihydrotestosterone, and carry out the first step in glucocorticoid clearance, generating 5β-dihydrocortisol from cortisol. 5β-reductase (AKR1D1) is also able to carry out the first step of glucocor...

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver 5β-reductase (AKR1D1) catalyses a fundamental step in bile acid (BA) synthesis. BAs and BA intermediates are potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial role in NAFLD and HCC. Liver biopsies and serum samples were obtained from healt...