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Endocrine Abstracts (2010) 24 S21

BSPED2010 Speaker Abstracts Symposium 3 – The Beta cell (3 abstracts)

Altered beta-cell signalling and congenital hyperinsulinism of infancy (CHI)

M Dunne


University of Manchester, Manchester, UK.


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 (ABCC8, KCNJ11) or by metabolopathies in which defects in glucose metabolism lead to altered channel activity. In both situations, β-cells no longer rest and are constitutively active with elevated levels of intracellular Ca2+ due to inappropriate closure of KATP channels. In contrast, gain-of-function defects in ABCC8 or KCNJ11 are a cause of type 2 diabetes, and neonatal diabetes. Through studies of the function of β-cells isolated from more than 140 patients following surgery, we have now documented the relationship between loss of KATP channel function and the histopathophysiology of CHI. This approach has allowed us to characterise a spectrum of defects related to impaired ion channel function, identify subsets of patients in which CHI is unrelated to defects in KATP channels and to critically examine the properties of β-cells isolated from the pancreas of focal CHI patients. Through a greater understanding of the ionic basis of CHI we have initiated studies related to the rescue of KATP channels in β-cells from patients and have begun to explore the rational basis of new therapeutic opportunities.

Volume 24

38th Meeting of the British Society for Paediatric Endocrinology and Diabetes

British Society for Paediatric Endocrinology and Diabetes 

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