Hyperinsulinemic hypoglycemia (HH) is a consequence of unregulated insulin secretion by pancreatic b-cells and is a major cause of hypoglycemic brain injury and mental retardation. Congenital HH is caused by mutations in genes involved in regulation of insulin secretion, seven of which have been identified (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1 and HNF4A). Severe forms of congenital HH are c...

BACKGROUND Congenital hyperinsulinism (CHI) is a rare genetic disorder characterised by inappropriate insulin secretion in the face of severe hypoglycaemia. There are two histological subtypes of CHI namely diffuse and focal. Diffuse CHI is most common due to recessive mutations in ABCC8/KCNJ11 (which encode the SUR/KIR6.2 components of the pancreatic β-cell KATP channel) whereas focal CHI is d...

OBJECTIVE Congenital hyperinsulinism (CHI) is a rare but severe cause of hypoglycemia. The present study investigates the clinical presentation, therapeutic outcomes and genetic mutations of CHI in Chinese individuals over the past 15 years. METHODS The authors retrospectively reviewed one case in their department and 206 cases reported from January 2002 to October 2016 in China. PubMed, Ovid...

OBJECTIVE To understand the genetic etiologies of congenital hyperinsulinism (CHI) in a population of Saudi patients, and to explore genotype-phenotype characteristics. METHODS We retrospectively reviewed a cohort of 11 children with CHI presenting to King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia between March 2007 and February 2012. Mutational analysis (ABCC8 and KCNJ11...

KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11) and ABCC8 (ATP-binding cassette, subfamily C (CFTR/MRP), member 8) have been studied for association with type 2 diabetes in various ethnic populations with contradictory results. We performed a comprehensive meta-analysis for KCNJ11 rs5219, rs5210, rs5215, and ABCC8 rs757110 to evaluate the effect of these regions on geneti...

The genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the -cell ATPsensitive potassium (KATP) channel, control insulin secretion. Common polymorphisms in these genes (ABCC8 exon 16–3t/c, exon 18 T/C, KCNJ11 E23K) have been variably associated with type 2 diabetes, but no large ( 2,000 subjects) case-control stu...

Recessive inactivating mutations in the ABCC8 and KCNJ11 genes encoding the adenosine triphosphate-sensitive potassium (K(ATP)) channel subunit sulphonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel subunit (Kir6.2) are the most common cause of hyperinsulinaemic hypoglycaemia (HH). Most of these patients do not respond to treatment with the (K(ATP)) channel agonist diazoxide....

BACKGROUND Accurate molecular diagnosis of monogenic non-autoimmune neonatal diabetes mellitus (NDM) is critical for patient care, as patients carrying a mutation in KCNJ11 or ABCC8 can be treated by oral sulfonylurea drugs instead of insulin therapy. This diagnosis is currently based on Sanger sequencing of at least 42 PCR fragments from the KCNJ11, ABCC8, and INS genes. Here, we assessed the ...

AIMS/INTRODUCTION The adenosine triphosphate (ATP)-sensitive potassium (KATP) channel is a key component of insulin secretion in pancreatic β-cells. Activating mutations in ABCC8 encoding for the sulfonylurea receptor subunit of the KATP channel have been associated with the development of neonatal diabetes mellitus (NDM). The aim was to investigate clinical and functional characterization of t...

Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNP...