Endocrine Abstracts

NES2Y cells were derived several years ago from a patient following surgery for Congenital Hyperinsulinism (CHI). These cells have the inductive capacity to form insulin-secreting cells, but they are largely uncharacterized. The purpose of this study was to examine the expression and function of the ATP-binding cassette protein ABCG2 and to characterize the cells for their expression of markers of Side Population (SP) progenitor cells and Stellate Cells (SC). Cells were mainta...

Hyperinsulinism in Infancy (HI) is a potentially-lethal condition of neonates and during early childhood. For many years the pathophysiology of this disorder was unknown. Recent advances in genetics, histopathology and molecule physiology have now revealed the causes of HI in a large cohort of patients. This review focuses upon the relationship between the basis of HI and current treatment options. From defects in ion channel subunit genes to lesions in the control of pancreat...

Diazoxide is an agonist of ATP sensitive K+ (KATP) channels in beta-cells and is used in the treatment of hyperinsulinism caused by insulinomas or Hyperinsulinism in Infancy (HI). The responsiveness of patients to diazoxide is highly variable and complicated by side-effects which include hypertension and hypertrichosis. The aim of this study was to examine the actions of a novel benzothiadiazine-derivative, BPDZ-154, on beta-cell KATP channels and insulin release. W...

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. ...

Hyperpolarisation-activated cyclic nucleotide-gated channels (HCNCs). are selective for Na+/Ca2+ under physiological conditions and are responsible for the rhythmical electrical behaviour of pacemakers in the heart and brain. Their role in human pancreas has not been reported previously. Congenital hyperinsulinism of infancy (CHI) is an inherited disorder of inappropriate insulin secretion often caused by gene defects in the subunits of KATP ch...

Congenital hyperinsulinism (CHI) is characterised by unregulated insulin secretion from pancreatic β-cells. The most severe forms are associated with defects in SUR1 and Kir6.2 (encoded by ABCC8 and KCNJ11), which form KATP channels in β-cells. Diazoxide therapy often fails in the treatment of CHI and may be due to reduced cell surface expression of KATP channels. We investigated methods to increase surface expression of KATP<...

Congenital Hyperinsulinism (CHI) is primarily a β-cell disorder with an incomplete pathogenesis. The purpose of this study was to generate in vitro models of the disease for the purposes of investigating the relationship between gene defect and β-cell development and function. We obtained post-operative resections of pancreatic tissue from four patients with hyperinsulinism. The tissue was collagenase treated and maintained in cell culture condit...

Hyperinsulinism in Infancy (HI) is the most common cause of recurrent or persistent hypoglycaemia in early childhood, and manifests as either diffuse abnormalities of pancreatic beta-cell function (Di-HI), or focal adenomatous hyperplasia of beta-cells (Fo-HI). Di-HI is caused by defects in KATP channel genes ABCC8 (SUR1) or KCNJ11 (Kir6.2). Fo-HI arises from somatic loss of maternal heterozygosity resulting in the expression of paternally-derived mutation(s) in SUR1 or Kir6.2...