Endocrine Abstracts

Context: Glucocorticoids have adverse systemic effects which may predispose to cardiovascular disease. The effect of glucocorticoid use on cardiovascular disease has not been assessed.Objective: To test the hypothesis that users of exogenous glucocorticoids have a dose-dependent increased risk of cardiovascular disease; in particular, that supraphysiological doses will be associated with cardiovascular disease.Design: A cohort study using a record linkage database....

Prenatal dexamethasone (dex) administration in rats retards foetal growth, and programmes hyperinsulinaemia and glucose intolerance in adult offspring. This can be explained in part by increased hepatic gluconeogenesis, due to up-regulated glucocorticoid receptor (GR) expression, but may also involve impaired peripheral glucose disposal. In this model, we previously showed no increase in skeletal muscle GR, and have now examined GR and key metabolic genes in adipose tissue.</...

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been implicated in the pathogenesis of human obesity and insulin resistance through 11-oxoreductase activation of cortisol (F) from cortisone (E) stimulating adipocyte differentiation and hepatic glucose output. In its purified state however, 11beta-HSD1 is a dehydrogenase inactivating F to E. In patients with cortisone reductase deficiency we recently identified two inactivating mutations, delta29bp and R453Q, withi...

(This poster is based on OC38)...

Adipose exposure to glucocorticoids (GCs) results in visceral adiposity and insulin resistance. Only the unbound, free fraction of GC can diffuse into cells. Corticosteroid binding globulin (CBG) is the major GC carrier, binding 80–85% of circulating GCs with high affinity. Targeted proteolysis of CBG by neutrophil elastase (NE) significantly reduces CBG binding affinity. This suggests that neutrophil-mediated inflammation provides a regulatory mechanism for delivery of G...

Adipose exposure to glucocorticoids (GCs) results in visceral adiposity and insulin resistance. Only the unbound, free fraction of GC can diffuse into cells. Corticosteroid binding globulin (CBG) is the major GC carrier, binding 80–85% of circulating GCs with high affinity. Targeted proteolysis of CBG by neutrophil elastase (NE) significantly reduces CBG binding affinity. This suggests that neutrophil-mediated inflammation provides a regulatory mechanism for delivery of G...

Prostaglandin E2 acts via 4 GPCRs, EP1-4. EP2 regulates inflammation and has important roles in cardiovascular function, reproduction, and malignancy. GPCR signalling and trafficking are highly integrated as signals from the endomembrane can exhibit distinct profiles from the plasma membrane. Whether EP2 activity is spatially regulated and if this is modified by ligand bias is currently unknown. In HEK 293 cells, three selective EP2 ligands, butaprost, AH13205, and PGN9856i, e...

Section 1: Case history: A 57-year-old female shop assistant presented with a four week history of increasing thirst and lethargy. The patient also reported non-specific pain in her shoulders, ribs and hips. She was otherwise well with no past medical history. Systemic enquiry was unremarkable. On examination nothing abnormal was noted. Specifically there were no rashes, lymphadenopathy or hepatosplenomegaly. Joint examination was normal and there was no muscle tenderness or w...

Background: Elevated morning plasma cortisol is associated with multiple cardiovascular risk factors in metabolic syndrome. Epidemiological studies have also reported a positive association between plasma cortisol and coronary heart disease (CHD), although not all estimates are statistically significant (OR 1.10 (95% CI 0.97 to 1.25)) (Davey Smith et al. Circulation 2005). Importantly, observational studies are unable to infer causality and results may be confounded.<...

Background: Vascular impairment, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in humans with obesity, insulin resistance or Cushing’s syndrome. Similar endocrine disorders in horses, resulting in insulin resistance, are associated with laminitis, a dysfunction of the vasculature supplying the hooves, the mechanism of which is unclear. We hypothesised that horses with insulin resistance have both local and systemic evidence of vascul...