Endocrine Abstracts

Introduction: Focal congenital hyperinsulinism (F-CHI) is caused by dual-hit pathology, comprising a paternally-inherited ABCC8/KCNJ11 mutation and somatic loss of the maternal allele at chromosome 11p15. This leads to dysregulation of insulin secretion and β-cell overgrowth with a focal domain.Objectives: To compare the proliferative index (PI) of the F-CHI lesion and non-lesion pancreatic tissues to age-matched control pancreata and insul...

Background: Atypical congenital hyperinsulinism in infancy (CHI-A) represent patients who generally present symptoms of hypoglycaemia later in the neonatal period, are poorly responsive to medical intervention and have no known genetic cause of disease. Our objective was to compare the expression profiles of insulin and somatostatin in islets from patients with CHI-A, diffuse CHI (CHI-D) and age-matched control tissue.Methods and materials: CHI tissues w...

Background: In diffuse CHI (CHI-D) insulin release is uncontrolled due to mutations in the ABCC8/KCNJ11 genes. Increased rates of cell proliferation have also been reported, but the mechanisms responsible for this are unknown. We hypothesized that this may arise as a consequence of failure to terminate proliferation in the neonatal period. Here, we examined the proliferative index (PI) of islet cells in CHI-D patients and compared this with focal CHI (CHI-F) ...

Background/hypothesis: Congenital hyperinsulinism in infancy (CHI) mainly arises from mutations in ATP-sensitive potassium channel genes. However, the expression pattern of defects can be markedly diverse. In diffuse CHI (CHI-D) all islet cells express gene defects, whereas patients with focal CHI (CHI-F) only express defects in a localised region of islet cells due to loss of a maternally-imprinted locus. Here, we examined the properties of a novel population of CHI islet cel...

Introduction: Congenital Hyperinsulinism (CHI) is a heterogeneous condition caused by dysregulation of insulin secretion. Paternally inherited mutations in ABCC8 or KCNJ11 are associated with loss of the maternal 11p15 allele in focal CHI (CHI-F). CHI-F can be curative after selective lesionectomy. However, histological heterogeneity within the CHI-F lesions has not been previously reported. We aimed to examine the diversity in focal lesions and correlate wit...

Introduction: Congenital hyperinsulinism (CHI) may arise due to loss-of-function mutations in ABCC8 and KCNJ11 genes which encode subunits of ATP-sensitive potassium (KATP) channels. KATP channels couple nutrient metabolism with insulin secretion in pancreatic β-cells but are also located in enteroendocrine L- and K-cells and may play a role in the control of GLP-1 and GIP secretion respectively. More than 70% of patients with CHI h...