Permanent neonatal diabetes (PND), requiring insulin within the first months of life, is unexplained at the molecular level in most cases. It has very recently been shown that heterozygous activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive K(+) channel involved in the regulation of insulin secretion, cause PND. In the present study, we screened ...

BACKGROUND Permanent neonatal diabetes mellitus (PNDM) is a rare disorder, characterized by uncontrolled hyperglycemia diagnosed during the first 6 months of life. In general, PNDM has a genetic origin and most frequently it results from heterozygous mutations in KCNJ11, INS and ABCC8 genes. Homozygous or compound heterozygous inactivating mutations in GCK gene as cause of PNDM are rare. In con...

BACKGROUND Type 2 diabetes is a global problem that is increasingly prevalent in low and middle income countries including India, and is partly attributed to increased urbanisation. Genotype clearly plays a role in type 2 diabetes susceptibility. However, the role of DNA methylation and its interaction with genotype and metabolic measures is poorly understood. This study aimed to establish whet...

Congenital hyperinsulinism (CHI) is a complex heterogeneous condition in which insulin secretion from pancreatic β-cells is unregulated and inappropriate for the level of blood glucose. The inappropriate insulin secretion drives glucose into the insulin-sensitive tissues, such as the muscle, liver and adipose tissue, leading to severe hyperinsulinaemic hypoglycaemia (HH). At a molecular level, ...

OBJECTIVE Sulfonylureas (SUs) are effective at controlling glycemia in permanent neonatal diabetes mellitus (PNDM) caused by KCNJ11 (Kir6.2) mutations. RESEARCH DESIGN AND METHODS We report the case of a woman with PNDM who continued high doses of glibenclamide (85 mg/day) during her pregnancy. The baby was born preterm, and presented with macrosomia and severe hyperinsulinemic hypoglycemia r...

BACKGROUND Mutations in ABCC8 and KCNJ11 are the most common cause of congenital hyperinsulinism (CHI). Recessive as well as dominant acting ABCC8/KCNJ11 mutations have been described. Diazoxide, which is the first line medication for CHI, is usually ineffective in recessive ABCC8 mutations. We describe the clinical and molecular characterisation of a recessive ABCC8 mutation in a CHI patient t...

AIMS Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. METHODS We have performed a case-control association study inclu...

OBJECTIVE Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case-control stu...

ATP-sensitive potassium (KATP) channels link cell metabolism to membrane excitability and are involved in a wide range of physiological processes including hormone secretion, control of vascular tone, and protection of cardiac and neuronal cells against ischemic injuries. In pancreatic β-cells, KATP channels play a key role in glucose-stimulated insulin secretion, and gain or loss of channel fu...