Endocrine Abstracts

Cathepsin K is a cysteine protease known for its importance in bone remodelling. Inhibitors of cathepsin K are in clinical trials for osteoporosis treatment, but side effects included altered levels of related cathepsins in peripheral organs and in the central nervous system (CNS). Importantly, cathepsin K has been identified not only in osteoclasts but also in most epithelia and, recently, in brain parenchyma. Lately, we have also shown that cathepsin K deficiency in mice ind...

Methods: The diagnosis of Cushing’s Syndrome (CS) was made as per the prevalent endocrine society guidelines. CS patients with serum ACTH>15 pg/ml were considered as ACTH-dependent CS. Baseline ACTH (both inferior petrosal sinuses and peripheral) values were obtained, and since 2014, stimulated ACTH values (5 and 10 minutes post one unit iv vasopressin) were obtained as standard protocol. Prolactin corrected ACTH ratios were additionally being calculated since 2016. The h...

Introduction: The visceral adipose tissue-derived serine protease inhibitor (vaspin), a novel adipocytokine, has been widely reported to be associated with obesity and insulin resistance. Obesity induced chronic inflammatory process plays a pivotal role in insulin resistance and is characterized by the activation of NF-κB pathway and its target genes. The present study aims to investigate the effects of vaspin on NF-κB pathway and its target genes in basal and TNF-&#...

ApoB isoforms are components of the chylomicron, and of the atherogenic LDL and Lp(a) particles. Ex26 is exceptionally long at 7.57kb as most exons are <500bp. Ex26 is also the site of RNA editing, which generates the ApoB48 isoform instead of ApoB100. The first 3kb of ex26 contains 15 sequences matching the splice site consensus, which could be used in splicing, but are not. Splice sites matching the consensus but which are not used are called pseudosites. How the spliceos...

Neurokinin B has been traditionally regarded as a neuropeptide being confined to the CNS, with no peripheral expression. This situation was the cause of some confusion as its preferred receptor (NK3R) is found mainly on peripheral organs such as the portal vein, mesenteric vessels and the heart with relatively low levels in the brain. In 2000 our laboratory reported the placenta to be an abundant peripheral endocrine source of NKB, giving rise to significant plasma concentrati...

Annexin 1 (ANXA1) plays an important role in mediating the negative feedback effects of glucocorticoids on the HPA axis. In the anterior pituitary gland ANXA1 is localised mainly to the non-secretory folliculostellate (FS) cells. It is released from these cells by glucocorticoids and acts locally to suppress ACTH release from corticotrophs. Functional and histological studies suggest that the steroid-induced translocation of ANXA1 across the FS cell membrane is effected via me...

Background: Mutations in succinate dehydrogense-B (SDH-B) or von Hippel Lindau (VHL) genes can result in chromaffin tumours.Objective: To compare the clinical phenotypes of subjects developing chromaffin tumours as a result of SDH-B or VHL mutations.Subjects: Thirty-one subjects with chromaffin tumours. Sixteen subjects had SDH-B gene mutations and 15 subjects had a diagnosis of VHL.<p ...

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. ...

Pharmacokinetics and tolerability of a new a bioadhesive buccal testosterone tablet in testosterone deficient men.RJM Ross, A Jabbar, H Jones, B Roberts, K Dunkley, A Long, H Levine, DR CullenObjectives: A phase I single centre, open label study of the pharmacokinetics and tolerability of a buccal testosterone tablet (COL1621). Design: The study was approved by The South Sheffield Ethics Committee. Twelve testosterone deficient males were treated with the buccal tablet...

B-type natriuretic peptide (BNP) is a hormone secreted from the heart in response to volume load and serves clinically as a reliable biomarker in the diagnosis of cardiac dysfunction and heart failure. As patients with heart failure present an increased risk for developing diabetes, we aimed to investigate the role of BNP on parameters of glucose metabolism in a placebo-controlled crossover study performed in 10 healthy volunteers (25±1 years; BMI 23±1 kg/m2</su...