Endocrine Abstracts

Hypophosphatasia (HPP) is an inherited skeletal disease characterized by defective bone mineralization due to a deficiency in tissue-nonspecific alkaline phosphatase (TNALP). Patients with the severe infantile form of HPP have a poor prognosis that often results in high mortality by one year. Asfotase alfa is an approved therapy for HPP, while requires chronic injections to maintain efficacy. To develop a one-time gene therapy for HPP, we examined the safety and efficacy of AA...

Gastric inhibitory polypeptide (GIP) is a post-prandially secreted gut hormone that acts upon the GIP-receptor (GIPR), to stimulate insulin secretion. Animal studies indicate that GIP influences bone remodelling, and in humans, GIP administration decreases levels of bone resorption markers. However, the mechanisms by which GIP influences resorption remain to be elucidated. Therefore, we investigated how GIP (10nM) affects bone cell activity using primary human osteoclasts, hum...

Fibroblast growth factor 23 (FGF-23) is a phosphatonin produced by osteocytes in response to serum phosphate concentration. Immunoassays are widely employed to detect C-terminal fragments of FGF-23 (cFGF-23). Quantitative assays for intact FGF-23 (iFGF-23) measurement are also available. Causes of increased FGF-23 include Tumour Induced Osteomalacia (TIO), X-linked hypophosphataemic rickets (XLH) and end stage renal disease (ESRD). We observed that some individuals, with no id...

Marshall-Smith syndrome (MSS) is a congenital disorder affecting skeletal and neural development, due to mutations in the nuclear factor I/X (NFIX) gene. NFIX encodes a ubiquitously expressed transcription factor that regulates the expression of viral and cellular genes. To identify novel genes that are misregulated by NFIX mutations, RNA sequencing and proteomics analyses were performed on mouse embryonic fibroblast (MEF) cells derived from a repres...

Diacylglycerol kinase delta (DGKD) has been implicated in calcium homeostasis and nephrolithiasis by genome-wide association studies. We have previously demonstrated that alterations in expression of DGKD cause biased calcium-sensing receptor (CaSR) signalling in vitro. To further elucidate the physiological role of DGKD we examined the biochemical phenotype of a Dgkd-haploinsufficient (+/-) mutant mouse developed by the International Mouse Phenotyping Consor...

Background: Studies have established a link between vitamin D deficiency and susceptibility to and severity of COVID-19. Our study aims to evaluate the role of vitamin D supplementation in intensive care units (ICU) in patients with COVID-19.Methods: We conducted a retrospective analysis of patients admitted to ICU in a large tertiary centre. Data on serum vitamin D concentration and supplementation, mortality, hospital and ICU stay, electrolyte replacem...