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21st Joint Meeting of the British Endocrine Societies

Oral Communications


ea0003oc25 | Metabolism | BES2002

Programming of adult adipose tissue metabolism by prenatal glucocorticoids in the rat

Cleasby M , Walker B , Seckl J

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.</...

ea0003oc26 | Metabolism | BES2002

Impact of thiazolidinediones on cardiovascular disease risk factors

Marchetti A , Boyle P , King A , Olansky L , Lau H , Magar R , Martin J

Risk of cardiovascular disease is higher for patients with diabetes and dyslipidemia. Known risk factors include elevated triglycerides (TG), total cholesterol (TC), LDL, and low HDL. The log(TG: HDL), known as Atherogenic Index of Plasma (AIP), is inversely correlated with LDL particle size (r=-0.78) and provides another marker of coronary heart disease (CHD) risk. Low-risk CHD cohorts have negative AIP values; high-risk cohorts have positive values. Patients with type 2 diab...

ea0003oc27 | Metabolism | BES2002

A digenic basis for severe insulin resistance in a large UK kindred - cosegregation of mutations in PPAR gamma and PPP1R3

Gurnell M , Savage D , Agostini M , Barroso I , Rajanayagam O , Soos M , Ross R , Schafer A , O'Rahilly S , Chatterjee V

We have previously reported dominant negative missense mutations (P467L, V290M) in human PPAR gamma (peroxisome proliferator-activated receptor gamma) in association with severe insulin resistance, early onset type 2 diabetes and hypertension. In a large UK kindred, where the proband presented at age 15 years with severe insulin resistance (acanthosis nigricans, hyperinsulinaemia, PCOS), we have identified a novel heterozygous frameshift premature stop mutation in the PPAR gam...

ea0003oc28 | Metabolism | BES2002

Rosiglitazone inhibits insulin-mediated rise in angiotensinogen expression and angiotensin II secretion in human subcutaneous adipocytes

Harte A , McTernan P , Smith S , Barnett A , Kumar S

The renin-angiotensin system (RAS)is important for the regulation of blood pressure with its blockade shown to reduce the vascular complications of diabetes. Adipose tissue expresses the RAS system and may contribute to obesity associated hypertension. Our previous in vitro studies have demonstrated that in human adipose tissue production of both angiotensinogen (AGT) and the active metabolite angiotensin II are stimulated by insulin. The present study investigated the ...

ea0003oc29 | Metabolism | BES2002

Deleterious effect of non-esterified free fatty acids (NEFAs) on resistance artery endothelial function

Sainsbury C , Hillier C , Sattar N , Petrie J , Connell J

Elevated circulating concentrations of non-esterified free fatty acids (NEFAs) are observed in states of insulin resistance and may be associated with increased cardiovascular risk. We hypothesised that NEFAs directly impair endothelial NO bioavailability via increased oxidative stress, in addition to their proposed indirect effect via VLDL. The study was designed to investigate the effect of monounsaturated and saturated fatty acids on endothelium-dependent and -independent v...

ea0003oc30 | Metabolism | BES2002

Increased muscle oxidation of dietary lipid contributes to oestrogen-induced improvements in postprandial lipid metabolism

Masding M , Stears A , Gelauf C , Burdge G , Wootton S , Sandeman D

Aims: Endogenous and exogenous oestrogens have previously been shown to improve postprandial lipid metabolism, probably due to up-regulation of hepatic LDL receptors. We used stable isotope techniques to investigate the contribution of muscle oxidation of dietary lipid to this improvement.Methods: Matched groups of healthy premenopausal (n=8) and postmenopausal (n=8) women and postmenopausal women taking oestrogen replacement therapy (HRT;...

ea0003oc31 | Metabolism | BES2002

An interaction between ghrelin and a species of high-density lipoprotein

Beaumont N , #TM-M|#Tan|# , Skinner V , Ramesh B , Byrne D , Mikhailidis D , Bouloux P , Srai S , Vanderpump M

Ghrelin is an acylated peptide hormone that is expressed by a variety of tissues including the stomach, hypothalamus and kidney. Ghrelin produces a range of effects, including stimulating the release of growth hormone from the pituitary gland, and inducing feeding and obesity.The effects of some hormones can be altered by interactions with other proteins; so the aim of this project was to screen plasma for proteins that can bind ghrelin, as part of an i...

ea0003oc32 | Metabolism | BES2002

Regulation of leptin receptor cleavage

Maamra M , Bidlingmaier M , Postel-Vinay M , Wu Z , Strasburger C , Ross R

The leptin receptor (ObR) exists in multiple isoforms. In humans, there is no mRNA encoding soluble receptor (LBP). We investigated the hypothesis that human LBP can be generated by proteolytic cleavage of membrane anchored leptin receptors (ObRb and ObRa). LBP, of similar size to that previously detected in human serum, was detected in medium of cells transfected with ObRa by HPLC, Immunofluorometric assay, and Ligand mediated immunofluorometric assay, but not by ELISA. The L...