ESPE Abstracts

Background and aim: Metformin is widely used in Type 2 diabetes, with increasing reports of a potential bone protective role. We investigated the role of AMPK in mediating the effects of metformin on mesenchymal stem cell (MSC) differentiation to either osteoblasts or adipocytes.Methods: Confluent mouse MSCs (C3H10T1/2), wild type (WT) and AMPK knockout (KO) mouse embryo fibroblasts (MEFs) were treated with metformin(500 μM), AMPK-activator A769662(...

Background: Neonatal diabetes (NDM) is defined as diabetes developing before 6 months of age, affecting one in 100 000 live births. Permanent NDM is diagnosed in the first 6 months of life with no remission. The majority have a mutation in the ATP-sensitive potassium (KATP) channel (KCNJ11 in 31%, ABCC8 in 13%). Autosomal dominant and recessive forms are described. The majority of patients with NDM caused by KATP mutations respond to sulphonylureas.<p...

Background: In humans, the GHN gene transcription is under the control of a Locus Control Region (LCR) enhancer, HSI, located 14.5 kb 5′ to the hGHN promoter. POU1F1, a pituitary-specific transcription factor, plays an essential role in the specification of the somatotroph, lactotroph and thyrotroph lineages and the activation of GHN, PRL and TSH gene transcription. All POU1F1 mutations so far reported have been linke...

Introduction: Congenital hyperinsulinism (CHI) is the commonest cause of severe hypoglycaemia in early childhood but glycaemic characterisation remains scarce. Continuous glucose monitoring (CGM) offers a deep understanding of glycaemic control to understand disease burden, individualise patient care and inform therapeutic trials in CHI. Preliminary studies suggest inadequate accuracy and no efficacy of standalone CGM to reduce hypoglycaemia. Provision is hist...

Objective: This project aims to evaluate the effect of two isotopically labelled internal standards on the quantification of 17OHP by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) as an orthogonal technique.Methods: Three LC-MS/MS and one GC-MS/MS laboratories, spanning four countries worldwide, who routinely measure serum17OHP, compared two internal ...

Objective: This project aims to evaluate the effect of two isotopically labelled internal standards on the quantification of 17OHP by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) as an orthogonal technique.Methods: Three LC-MS/MS and one GC-MS/MS laboratories, spanning four countries worldwide, who routinely measure serum17OHP, compared two internal ...

CRN04777 is an orally administered nonpeptide that is a potent and selective agonist of somatostatin 5 (SST5) receptors and is currently under development for the treatment of congenital hyperinsulinism (HI), the most common cause of persistent hypoglycemia in newborns and infants. Congenital HI arises from mutations within the insulin secretion pathway and is characterized by excessive and/or inappropriate insulin secretion by pancreatic islet beta cells. This excess insulin ...

Background: During early bone formation, mesenchymal stem-cells condense and differentiate into collagen type 2-expressing chondrocytes which form the cartilaginous bone anlagen. This anlage becomes enclosed by the perichondrium. The perichondrium consists of two layers, the inner cambium layer containing chondrocyte- and osteo-precursor cells and the outer fibrous layer important for mechanical and structural support. While the regulation of the growth plate is increasingly w...

Introduction: Nephroblastoma or Wilms tumor is the most common pediatric abdominal malignancy. Typically, it is found in children younger than 5 years old, girls being more likely to have Wilms tumor than boys. The etiology of the disease is genetic, due to alteration in the development of the genitourinary tract.[1] Treatment is represented by surgery (unilateral nephrectomy), chemo- and radio-therapy. Paraneoplastic endocrine disorders may occur, but there a...

Background: Heterozygous mutations in the Aggrecan gene (ACAN) cause autosomal dominant short stature with bone age (BA) acceleration, and premature growth cessation.Objective and methods: To characterize the phenotypic spectrum, associated conditions and describe response to growth-promoting therapies, detailed clinical evaluation of 73 mutation positive individuals from 16 families different families with heterozygous ACAN mutations was perfor...