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 (...

The opposite phenotypes of diabetes and hyperinsulinism can be caused by different types of mutations within the same genes. For example, rare activating GCK gene mutations cause hyperinsulinism whereas the more common loss-of function mutations result in mild fasting hyperglycaemia in the heterozygous state or recessively inherited permanent neonatal diabetes.The knowledge that inactivating mutations in the KCNJ11 and ABCC8 genes en...

Neonatal diabetes or monogenic diabetes of infancy can manifest as a transient or permanent condition. TNDM is most commonly caused by imprinting disorders on chromosome 6q24 (TNDM1.Uniparental Isodisomy Chromosome 6, Paternal Duplication of 6q24, loss of maternal methylation). Recently it has been identified that over half of those with maternal hypomethylation at 6q24 have relaxed maternal methylation at other imprinted loci and that the majority of these patients have mutat...