Endocrine Abstracts

Background. The endothelial dysfunction prevalent in hypertension and diabetes is associated with an imbalance in the levels of nitric oxide (NO) and superoxide (SO). NAD(P)H oxidase is the predominant source of SO in the vasculature. Objectives. To manipulate levels of SO using the NAD(P)H oxidase inhibitors, apocynin, phenyl arsine oxide (PAO) and 4(2aminoethyl)benzenesulfonyl fluoride (AEBSF) and relate this to NO bioavailability. Methods. NO bioavailability was compared in...

Glucocorticoids (Gc) are highly potent anti-inflammatory agents. They act through the glucocorticoid receptor (GR), a protein capable of multiple protein interactions. The pro-inflammatory cytokines, TNF-a and IL-1 signal, in part, through activation of NF-kB. Nf-kB transactivation is inhibited by activated GR. It has been suggested that the GR, and the p65 (RelA) component of NF-kB form a direct contact independent of Gc ligand, and that Gc binding results in inhibition of p6...

Raised levels of IGF-I have been associated with risk of developing several cancers including breast carcinoma. In addition to promoting mitogenesis in breast cancer cells, a number of observations suggest a role for inhibition of apoptosis by IGF-I receptor activation. Ligand binding to IGF-IR leads to activation of both the phosphoinositide-3'-kinase (PI3K) and the Ras/Raf/MAPKinase pathways. Deprivation of serum growth factors induces apoptosis in MCF-7 breast cancer cells ...

The release of cytochrome c from mitochondria is often the trigger for the nuclear and cytoplasmic changes that characterise apoptotic cell death. Previously, we have shown that vascular endothelial cells of the line, EA.hy 926, undergo apoptosis in response to TNFalpha, camptothecin and oxidants and that this is blocked by the glucocorticoid, dexamethasone (Dex). As a tool to determine where in the apoptotic pathway Dex acts to block the apoptotic process, we have developed a...

Voltage-gated calcium channels (VGCC) play a fundamental role in the control of insulin secretion from pancreatic B-cells since they govern rises in cytosolic Ca2+ in response to depolarization-dependent agonists, such as glucose. Here, we have examined the function and expression of VGCC in human B-cells. We isolated tissue from patients with B-cell adenoma (AD) and Hyperinsulinism in Infancy (HI) following surgery and used transplantable human islets as controls. ...

Background: Mutations in the GHR result in extreme short stature (Laron's syndrome). We have studied mutations from two patients with Laron's syndrome. Patient 1 (GHRextra) has a mutation in the GHR extracellullar domain due to a 108bp inframe pseudoexon between exons 6 and 7. Patient 2 (GHRintra) has a 22bp deletion in exon 10 of the GHR leading to premature termination of the GHR upstream of the intracellular STAT5 binding site.Aim: To compare GHR str...

Human obesity is characterised by an increase in both the number of adipocytes and by an increase in their size, which is determined by adipogenesis. Adipogenesis can be induced in vitro in preadipocytes cultured in differentiation medium containing 3-isobutyl-1-methylxanthine, insulin, dexamethasone, and triiodothyronine but the signalling pathways important in adipogenesis are not well characterised. The p38 mitogen-activated protein kinase (MAPK) signalling pathway i...