Endocrine Abstracts

Hypertension is a common feature of patients with type 2 diabetes, and contributes to the markedly increased risk of cardiovascular disease associated with the diabetic state. Both hypertension and type 2 diabetes are features of the Insulin Resistance Syndrome. Susceptibility genes for the development of the Insulin Resistance Syndrome could contribute to the close association between hypertension and type 2 diabetes. Support for this concept comes from the identification of ...

While organisms have evolved to maintain the fidelity of their genome, the epigenome, in contrast, is inherently plastic, with extensive remodeling required during normal development. This epigenomic plasticity plays a role in preparing the developing organism for its adult environment. The epigenome is able to sense environmental cues, providing an opportunity for adaptive changes during development that can provide a later-life survival advantage. However, epigenomic plastic...

In Cushing's Syndrome, elevated circulating cortisol levels are responsible for the association of central obesity, hypertension, insulin resistance, hyperglycaemia, and dyslipidaemia. Recent evidence suggests that there are subtle elevations in circulating cortisol concentrations amongst patients with hypertension and insulin resistance, and these are predicted by low birthweight suggesting that they may be programmed by events occurring in early life. In addition, there is e...

The hypothalamic-pituitary adrenal (HPA) axis plays a key role in the metabolic response to stress, so it is to be anticipated that cortisol signalling might in turn be regulated by nutritional status. This regulation might operate either centrally, controlling ACTH and hence plasma cortisol, or peripherally, controlling metabolism of cortisol in target tissues.Plasma cortisol levels are elevated during starvation in animals and a recent meta-analysis co...

Similarities between the metabolic syndrome and Cushing’s syndrome, and reversibility of the features of Cushing’s syndrome, suggest that cortisol may contribute to pathophysiology in both conditions and that reducing cortisol action may provide a novel therapeutic approach in metabolic syndrome. There is substantial evidence that circulating cortisol concentrations are higher in people with hypertension and glucose intolerance. The basis for t...

Several enzymes are expressed in adipose tissue which catalyse interconversion of steroids, generating oestrogens (aromatase), androgens (5α-reductase 1), and glucocorticoids (11β-HSD1). These steroids may activate local receptors which influence body fat accumulation and distribution, or be secreted to exert endocrine effects. Several mouse models (e.g. aromatase and 11β-HSD1 knockout mice and studies with 11β-HSD1 inhibitors) illustrate the potential impo...

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been implicated in the pathogenesis of human obesity and insulin resistance through 11-oxoreductase activation of cortisone (E) to cortisol (F) within the endoplasmic reticulum (ER) of adipocytes and hepatocytes. In its purified state 11beta-HSD1 is principally a dehydrogenase, converting F to E. Oxo-reductase activity can be regained by the addition of an NADPH regeneration system. In vivo hexose-6-phosphate ...

Endokinin B (EKB) is a recently identified tachykinin whose role is not yet fully understood. EKB displays equivalent affinity for the three tachykinin receptors as substance P (SP) which it is often found co-expressed with. SP has been implicated in a variety of neuroendocrinological responses including stress regulation, and affective and anxiety-related behaviours. An important aspect, therefore, is to dissect a distinct role for EKB from that of SP. Here, we have attempted...

Alterations in the rate of glucocorticoid(GC) metabolism induce compensatory changes in GC secretion under the control of the hypothalamic-pituitary-adrenal (HPA) axis. The principal routes of metabolic clearance of GCs are by hepatic A-ring reduction however the regulation of these enzymes is poorly understood. Recently we and others have demonstrated that bile acids act as potent inhibitors of GC metabolism by 5beta-reductase and 11beta-hydroxysteroid dehydrogenases in vi...

Introduction: Charcot neuroartropathy (CN) is a devastating complication of diabetes rapidly leading to irreversible foot deformity when misdiagnosed. Differential diagnosis with foot infections and other foot-related diseases remains challenging.Case: A 58-year-old woman with type 2 diabetes was hospitalised with a red, swollen left leg and high fever. The diagnosis of erysipelas with a neuropathic wound of the first digit as the entry wound was establi...