Endocrine Abstracts

Inhibiting 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) has been proposed to prevent local regeneration of cortisol from cortisone, and thus enhance hepatic and adipose insulin sensitivity. In healthy men and patients with type 2 diabetes, the non-selective 11HSD inhibitor carbenoxolone enhances hepatic insulin sensitivity but, paradoxically, does not increase peripheral glucose disposal. In obesity, 11HSD1 activity and mRNA are increased in adipose biopsies. We tested ...

A 22 years old woman presented with a few days history of nausea, vomiting and general lethargy. She was not on any treatment except the oral contraceptive pill (OCP). She was apyrexial, tachycardic at 140/min with a regular pulse and her blood pressure was 110/70. She was not pigmented. Her plasma sodium was 131 mmol/l, with normal potassium, creatinine and urea. Her arterial blood gas analysis showed a pH of 7.22 and bicarbonate of 12mmol/L. Her TFTs showed a thyrotoxic pict...

Obesity is associated with hypothalamic-pituitary-adrenal (HPA) axis activation. In obese humans and leptin-resistant obese Zucker rats, we have reported increased excretion of A-ring reduced glucocorticoid metabolites. We have now investigated regulation of hepatic A-ring reductases in the obese Zucker rat.Lean and obese Zucker rats (9wks) were studied either: 3-weeks after adrenalectomy (ADX) or sham surgery; or after 3-weeks treatment with metformin ...

Introduction: Copeptin is the C-terminal fragment of proAVP and provides an alternative measure of AVP secretion. While direct measurement of AVP during hypertonic saline infusion has been recommended as a diagnostic test for diabetes insipidus (DI), the number of reports examining the utility of copeptin in this context is limited. Here we describe a series of cases where measurement of copeptin during saline infusion has contributed to ...

Introduction: Copeptin is the C-terminal fragment of proAVP and provides an alternative measure of AVP secretion. While direct measurement of AVP during hypertonic saline infusion has been recommended as a diagnostic test for diabetes insipidus (DI), the number of reports examining the utility of copeptin in this context is limited. Here we describe a series of cases where measurement of copeptin during saline infusion has contributed to ...

Background: Adipose tissue dysfunction could partially explain the well-demonstrated association between obesity and survival in breast cancer (BC). Oestrogen and glucocorticoid concentrations and their respective activation enzymes, oestrogenic 17β-hydroxysteroid dehydrogenases (17βHSDs) and aromatase, and 11βHSD1 are increased in adipocyte hyperplasia and hypertrophy, supporting the hypothesis of a potential role for locally generated steroids in obesity-assoc...

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...

Previously, we have shown that 5α-tetrahydrocorticosterone (5αTHB), the reduced metabolite of corticosterone (B, the main glucocorticoid in rodents), binds to the glucocorticoid receptor, suppresses the HPA axis but has weak in vivo effects on adipose tissue and liver metabolism. Here we have compared the anti-inflammatory effects of B and 5αTHB in three in vitro and in vivo experiments. Cytokine release was measured by cytometric bead array...

Background: In mice, a methionine-choline deficient diet (MCDD) causes steatohepatitis and hepatic insulin resistance. In contrast, a simple choline-deficient diet (CDD) causes liver fat accumulation without steatohepatitis, insulin resistance or weight loss. We hypothesised that differences in liver and adipose fatty acid metabolism underlie the contrasting predisposition to steatohepatitis and hepatic insulin resistance.Methods: C57Bl6 mice (male, aged...

The major glucocorticoids (cortisol in man and corticosterone in the rat) play an important role in obesity and its attendant hypertension. However, there is no consistent evidence of glucocorticoid excess in simple obesity, suggesting that its role in the regulation of adipose tissue mass results from a more complex mechanism than adrenal hypersecretion of glucocorticoid. Glucocorticoid biosynthesis is not limited to the adrenal cortex; mRNA and enzymatic activity of 11β...