Endocrine Abstracts

11beta-hydroxysteroid dehydrogenase type 1 (11B-HSD1) catalyses the inter-conversion of cortisone and cortisol, and has been implicated in the pathogenesis of a number of disorders including insulin resistance and obesity. The enzyme is a glycosylated membrane-bound protein, located in the lumen of the endoplasmic reticulum (ER) and has proved difficult to purify in an active state. Previously, we reported the successful expression and purification of human 11B-HSD1 from E. co...

Impaired insulin action is a characteristic feature of type 2 diabetes and skeletal muscle is the principal tissue for peripheral glucose disposal. Aims: To determine if after prolonged culture human muscle cells from characterised type 2 diabetes patients have defects of insulin action compared to controls. Design: After attaining local Ethical Committee approval six compliant type 2 diabetic patients with severe clinical insulin resistance, on greater than 100 units of insul...

Impaired insulin action is a characteristic feature of type 2 diabetes and skeletal muscle is the principal tissue for peripheral glucose disposal. Aims: To determine if after prolonged culture human muscle cells from characterised type 2 diabetes patients have defects of insulin action compared to controls. Design: After attaining local Ethical Committee approval six compliant type 2 diabetic patients with severe clinical insulin resistance, on greater than 100 units of insul...

A 61 year old woman presented with a six months history of nausea, vomiting and lethargy. She is a non-smoker and drinks little alcohol. She was on 100mcg of Thyroxine following partial thyroidectomy. Physical examination was unremarkable apart from postural hypotension (BP 140/80mmHg laying, 105/75mmHg standing). Blood tests showed plasma sodium of 121mmol/L with normal potassium, urea, creatinine, FBC, random glucose and TFTs. A short synacthen test (1mcg) was normal with a ...

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 ...

Glucocorticoids are potentially important in obesity; recent data suggest both circulating levels and tissue-specific changes in glucocorticoid responsiveness and metabolism may influence their effect. In obese Zucker rats, the phenotype is ameliorated by adrenalectomy, and shows the same pattern of altered glucocorticoid metabolism as in human obesity. However, previous reports suggest hepatic glucocorticoid receptor (GR) binding is impaired. We have now explored expression o...

Background: The National Paediatric Diabetes audit (NPDA) reports increasing number of children and young people with type 2 diabetes (CYP2D). CYP2D are less likely to receive all recommended health checks compared to those with type 1 diabetes (33% vs 59% respectively) and do not receive treatment for complications even when they are identified (T2D spotlight audit 2019/20). We assessed variation in care across different units against the national T2D guideli...

Introduction: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders that arise from enzyme deficiencies in biosynthetic pathways of the adrenal. The most common enzyme deficiency, 21-hydroxylase deficiency, results in cortisol deficiency, androgen excess and variable aldosterone deficiency. Current guidelines recommend a standard dose short Synacthen test (SDSST) is performed between 24 and 48 hours of life, with measurement of corti...

Control mechanisms of adrenocorticotrophic hormone (ACTH) and cortisol (CORT) secretion and metabolism during acute systemic inflammation (e.g. major surgery) have never been clearly elucidated. We sampled blood every 10 minutes for 12 h during and after coronary artery bypass grafting (CABG) in 10 patients to create profiles of ACTH, CORT and inflammatory mediators and compared these to healthy controls. Patients’ ACTH and CORT responses were classified into one of three...

Background: Glucocorticoids (GCs) modulate glucose homeostasis by acting on metabolic tissues including liver, adipose, and skeletal muscle. ABCC1 is a transmembrane ‘drug-resistance’ transporter expressed in adipose tissue and skeletal muscle with previously unknown physiological function. We recently showed that ABCC1 modulates intracellular GC concentrations and action in adipose. Here, we tested the hypothesis that Abcc1 regulates GC concentrations in skeletal mu...