Endocrine Abstracts

Foot complications are common in people with diabetes. As the incidence of diabetes continues to rise and an increasingly aged population accrue substantial numbers of non-reversible, chronic disease processes, the burden of diabetic foot disease can only grow. Ulceration and amputation are associated with high mortality, reduced quality of life and significant financial cost to both patient and health care provider.The management of diabetic foot diseas...

Pro-opiomelanocortin (POMC) deficiency in mice and humans results in a syndrome of severe obesity, hyperphagia and adrenal insufficiency. We have used mice heterozygous for a null mutation in the Pomc allele (Pomc+/-) to determine if POMC haploinsufficiency results in disordered energy homeostasis or adrenal hypofunction.When fed standard lab diet (SLD, 4.5% fat) Pomc+/-were similar in weight to wild type (WT) mice thr...

Inactivating mutations of the POMC gene in humans and mice result in a complex phenotype of hyperphagia, obesity and glucocorticoid (GC) deficiency, but without many features of metabolic syndrome. We have previously shown that replacement of GC in Pomc−/− mice exacerbates their hyperphagia, increases fat mass and elevates plasma leptin and insulin. We have now examined key determinants of glucocorticoid action, including glucocorticoid receptor (...

A 75-year-old female presented with 12kg weight loss and malaise, 18 months after a diagnosis of type 2 diabetes mellitus. Abdominal CT scanning demonstrated bilateral adrenal masses and her symptoms responded rapidly to empirical treatment with dexamethasone. CT guided biopsy demonstrated adrenal hyperplasia.Centripetal weight distribution and proximal myopathy were prominent, and serum cortisol failed to suppress following standard 48h low dose (662nm...

Glucocorticoids are widely prescribed therapeutic agents, however long term treatment can cause increased morbidity from adverse metabolic events, including weight gain and hyperglycaemia. The mechanisms and site of action which underpin these side-effects are not fully understood. The aim of this study was to characterise phenotypic, biochemical and neurohormonal responses in mice administered corticosterone, with a particular focus on changes seen in the early stages of chro...

Glucocorticoids (Gcs) are used in the treatment of inflammatory disorders including asthma and rheumatoid arthritis. However, long-term use can cause metabolic side-effects including obesity and diabetes. Previous studies have shown that Gcs increase Agrp expression and that AgRP/NPY/GABA (ANG) neurons can regulate appetite and insulin sensitivity. To investigate the effects of chronic Gc treatment directly on ANG neurons, we crossed AgRP-IRES-Cre with GR...

Glucocorticoid (Gc) excess, either from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects including obesity, hyperphagia, and hyperglycemia. The Gc receptor (GR) is widely expressed in the brain including the hypothalamus which is known to regulate energy balance. We have previously established through the administration of corticosterone (Cort) in the drinking w...

Glucocorticoids (Gcs) are widely prescribed to treat a number of conditions, such as arthritis and asthma. However, patients receiving Gcs often develop metabolic complications such as obesity and hyperglycaemia. The aim of this study was to investigate the molecular mechanisms in the hypothalamus which drive these adverse effects. Male C57BL/6J mice were given ad libitum access to either corticosterone (CORT; 75 μg/ml) or vehicle (V; 1% ethanol) in their drinkin...

Recently, rare loss-of-function mutations of melanocortin-2-receptor accessory protein 2 (MRAP2) have been associated with severe, early-onset obesity in humans. In addition, whole body deletion and targeted brain specific deletion of the Mrap2 gene resulted in severe obesity in mice. In vitro data have shown Mrap2 interaction with the melanocortin-4-receptor (MC4R) affecting receptor signalling as a consequence. However, the mechanism by which Mrap2...

Glucocorticoid (Gc) excess, either endogenously produced (Cushing’s syndrome) or as a result of exogenous steroid treatment, can cause metabolic disorders such as obesity and hyperglycaemia. The contribution of centrally acting corticosterone in the development of these metabolic disorders is unknown. Gcs regulate the anorexigenic and orexigenic neuropeptides (POMC and AgRP) within the arcuate nucleus of the hypothalamus to modulate energy balance. This study investigated...