Endocrine Abstracts

The calcium-sensing-receptor (CaSR) is a G-protein-coupled receptor that plays a fundamental role in extracellular calcium homeostasis, but is also implicated in non-calcitropic disorders including colon cancer and asthma. In addition, CaSR is highly expressed in pancreatic islets where it has a role in insulin secretion. Patients with gain-of-function CaSR mutations, and mice (referred to as Nuf) with a gain-of-function CaSR mutation (Leu723Gln), develop autosomal dominant hy...

To identify genes causing hypercalciuria, we screened male offspring of C57BL/6J male mice mutagenised by N-ethyl-N-nitrosourea (ENU) for this abnormality. Mice were kept in accordance with UK Home Office welfare guidelines and project licence restrictions. Metabolic cage studies were performed to collect 24-hour urine samples, and this revealed one mouse with hypercalciuria (Hcalc1). Inheritance testing demonstrated that Hcalc1 was inherited as an autosomal domi...

Familial hypocalciuric hypercalcaemia type 1 (FHH1) is mainly caused by loss-of-function missense mutations of the extracellular calcium-sensing receptor (CaSR), which is a parathyroid- and kidney-expressed G-protein coupled receptor that plays a pivotal role in mineral metabolism. Here, we report the unusual occurrence of a novel heterozygous in-frame CASR exon 4 deletion, c.(492+1_493-1)_(1377+1_1378-1)del, in a family with FHH1. This mutation is predicted...

Introduction: New therapeutic strategies are urgently needed to improve radioiodide (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. We recently utilised high throughput screening and identified FDA-approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. Categorisation revealed a high proportion of drugs that modulate proteostasis, with 6 of the top 15 targeting activity of...

Dysregulation of sodium-iodide symporter (NIS) function is common in differentiated thyroid cancer, resulting in sub-optimal radioiodide therapy and poorer clinical outcome. Recent developments in identifying proteins that regulate the function of the sodium iodide symporter have highlighted two proteins involved in internalisation of NIS from the plasma membrane: AP-2 and moesin. Clathrin-mediated endocytosis (CME) of NIS is facilitated through the adaptor protein 2 (AP2) com...

Background: Current therapies for reducing raised intracranial pressure (ICP) in conditions such as idiopathic intracranial hypertension have limited efficacy and tolerability. As such, there is a pressing need to identify novel drugs. Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat diabetes and promote weight loss but have also been shown to affect fluid homeostasis in the kidney. Here, we investigate whether exendin-4, a GLP-1R agonist, is able to modula...

Background: Current therapies for reducing raised intracranial pressure (ICP) in conditions such as idiopathic intracranial hypertension have limited efficacy and tolerability. As such, there is a pressing need to identify novel drugs. Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat diabetes and promote weight loss but have also been shown to affect fluid homeostasis in the kidney. Here, we investigate whether exendin-4, a GLP-1R agonist, is able to modula...

The proto-oncogene pituitary tumor-transforming gene-binding factor (PBF) is upregulated in multiple tumours including thyroid cancer. PBF overexpression mediates tumorigenic processes such as cell motility and accelerates thyroid cancer cell invasion. We have recently shown that both PBF phosphorylation at tyrosine 174 (Y174) and PBF endocytosis are required for PBF-stimulated thyroid and breast cancer cell migration and invasion. This prompted further investigation into a ph...

Context: Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure and occurs predominantly in obese premenopausal women. Signs and symptoms of polycystic ovary syndrome (PCOS) often coexist in IIH. Here we compared the androgenic and metabolic phenotypes in IIH, PCOS and simple obesity.Patients and Methods: We studied 25 patients with IIH (mean age 34.4±9.2 years; mean BMI 37.8±5.2 kg/m2), in comp...

Introduction: Paediatric obesity is a growing concern for the health service. There is currently no consensus for routine screening of metabolic profiles and medical treatment in obese paediatric patients.Aims/methods: We aimed to determine medium-term outcomes of Metformin treatment on BMI, glucose and insulin levels in obese paediatric patients. In a retrospective review, data were collected from obese paediatric patients on Metformin for insulin resis...