Endocrine Abstracts

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.</...

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...

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...

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 ...

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...

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;...

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...

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...