Endocrine Abstracts

Ion channels play a key role in the regulation of insulin release. Conveying the signals associated with glucose metabolism, ATP-sensitive potassium (KATP) channels induce a depolarisation of the cell membrane which in turn regulates Ca2+ influx and Ca-dependent exocytosis of insulin-containing granules. Congenital hyperinsulinism is caused by channelopathies through loss-of-function mutations in the genes which encode KATP channels (...

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...

Objectives: Delayed puberty is thought to be common in boys with Duchenne muscular dystrophy [DMD]. To date, studies addressing its frequency are not available. This study aims to report the frequency of delayed puberty in DMD from clinical examination.Methods: All boys with DMD aged at least 14 years in January 2022 known to the Glasgow paediatric neuromuscular service (2015-2022) were included. Thirty-seven boys were identified. All 37 boys had at leas...

Introduction: There is a need to understand testicular development in adolescents with Duchenne Muscular Dystrophy (DMD).Objective: To evaluate testicular development and function in DMD over 12 months.Methods: All data are presented as median(range). 23 boys aged 12.4 years (10.0, 16.8) with a bone age delay of 0.9 years (−2.4, 7.1) had physical and biochemical assessment of puberty at Month 0(M0) and Month 12(M12) and divid...

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...

ATP-evoked signalling events are known to promote release of insulin from pancreatic beta-cells in a Ca2+-dependent manner. In rodent beta-cells and insulin-secreting cell lines, this is mediated by purinergic receptors and there is evidence for the involvement of both P2X and P2Y subtypes. Here,we have used human insulin-secreting cells to examine the expression of purinoceptors in control and disease tissue. Intact islets and isolated beta-cells were obtained from...

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<...