Endocrine Abstracts

Hypoglycaemia is an almost unavoidable consequence of iatrogenic insulin therapy in type 1 diabetes. Recurrent hypoglycaemia (RH) results in suppression of normal counter-regulatory hormonal and physiological responses (CRR) to future episodes increasing the risk of severe hypoglycaemia. The mechanisms responsible for this phenomenon remain unclear but may reflect changes in critical hypothalamic glucose sensing neurons (GSN). We set out to indirectly test the hypothesis that ...

Background: Obesity is a major medical health problem. Human brown adipose tissue (BAT) is potently activated by cold exposure and is a potential novel anti-obesity target. The current gold standard for measuring BAT activity in humans is 18F-FDG PET/CT. However it has two major limitations – exposure to ionizing radiation and high cost. Since BAT is a thermogenic organ located in the supraclavicular and neck regions, we hypothesised that an increase in tempera...

Background: The 5α-reduced glucocorticoid, 5α-tetrahydrocorticosterone (5α-THB), displays a dissociated steroid profile exhibiting anti-inflammatory effects in a murine model of thioglycollate-induced peritonitis but failing to induce adverse metabolic effects caused by corticosterone. We assessed the topical anti-inflammatory properties of 5α-THB in a model of irritant dermatitis. Given the adverse effects of steroids on cutaneous wound healing, we also in...

Background: 5α-reductase 1 (5αR1) metabolises steroids such as glucocorticoids and androgens, and is highly expressed in murine liver. Genetic disruption of 5αR1 leads to adverse metabolic changes in mice. We hypothesised that dutasteride, a 5αR inhibitor, induces insulin resistance in mice, as in humans, and this effect is underpinned by increased hepatic glucocorticoid action; an experimental paradigm was set up using A-348441, a liver-selective glucocort...

Background: Obesity is a global health concern. Elevating energy expenditure (EE) would be a highly effective treatment approach to treat obesity but no current drugs can safely achieve this. Cold exposure potently increases EE through brown adipose tissue (BAT) thermogenesis in humans. Glucagon elevates EE via BAT in rodents but the mechanism in humans is unknown. We investigated for the first time the mechanism by which glucagon increases EE in humans....

Specific variations in the human glucocorticoid receptor (GR) gene associate with increased cardiovascular disease risk. GR signalling is essential for cardiac maturation in utero and adult mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice) have cardiac hypertrophy, fibrosis and impaired function. Intriguingly, levels of left ventricle (LV) mRNA encoding the mineralocorticoid receptor (MR), which is pro-fibrotic in heart, rise postnatally ...