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...

Tumour necrosis factor-alpha (TNF-α) is a pleiotropic cytokine well characterised as a mediator of skeletal muscle wasting. However, the role of interlukin-6 (IL-6) in skeletal muscle remains controversial.Objectives: We therefore investigated the potential interactive effects of TNF-α and IL-6 on murine C2 skeletal myoblast survival, differentiation and proliferation.Methods: Real time-PCR, creatine kinase assay, western...

Introduction: Prolonged elevations of proinflammatory cytokines are associated with sarcopenia muscle wasting (ageing) and in cancer cachexia. Increased activation of the IGF/insulin pathway is an attractive target for combating such wasting.Aims: Using rodent skeletal muscle cell lines we have investigated TNF-α/IGF-I interactions, in an attempt to mimic and understand mechanisms underlying skeletal muscle loss.Methods and re...

Primary hyperaldosteronism is now recognised as the most frequent underlying cause of hypertension. We recruited 94 patients (age (mean±S.D.) 56±11 years) with hypertension from primary care in order to study the role of corticosteroid hormone action in this cohort. Random, blood pressure (BP), plasma renin activity (PRA) and aldosterone (Aldo) was measured both on and off antihypertensive medication. In addition, a 24 h ambulatory blood pressure (ABP)...

The epidemic of obesity, insulin resistance and type 2 diabetes has heightened the need to understand the mechanisms that contribute to their pathogenesis. Endogenous glucocorticoid (GC) production and metabolism have been implicated based upon parallels with Cushing’s syndrome. The interaction between GC metabolism and insulin sensitivity in the context of significant weight loss has not been explored. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that gen...

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...

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...

ACRD presents with clinical features of hyperandrogenism in females similar to those of PCOS (acne, hirsutism, oligomenorrhea, infertility), and precocious puberty in males. Obesity also occurs in some cases. Increased cortisol clearance leads to an increased hypothalamic-pituitary-adrenal axis drive resulting in elevated serum androgen levels and a decreased urinary cortisol metabolite: cortisone metabolite ratio below 0.5 (normal adult range 0.7–1.3). These observations...

In response to the 2003 Government White Paper entitled ‘Our future, Our inheritance’, we piloted a project to promote the genetic service within tertiary medicine. Three clinical nurse specialists (CNS); renal, cardiac and endocrine, are the catalyst for interaction between disciplines. This abstract relates the endocrine genetic experience.Targeting patients and families with genetic endocrine disease is achieved by three methods; identificat...