Abstract
Persistent Hyperinsulinemic Hypoglycaemia of Infancy (PHHI) is a metabolic syndrome of unregulated insulin secretion. It is a heterogenous disease with causes linked to mutations of the ATP sensitive potassium channels of the β cell, as well as to metabolism in the β cell. 5 candidate genes – ABCC8, KCNJ11, GCK, GLUD1 and SCHAD have been implicated in the disease so far, however the aetiology of the disease remains unknown in up to 50% of all patients. We genotyped 43 subjects with PHHI (20 surgically treated and 23 medically treated) for disease associated mutations in the candidate genes. Mutations on ABCC8 were identified in 16 of the 20 (80%) of the surgically treated patients. One putative mutation was identified in the medically treated cohort. The polymorphism E23K on KCNJ11 that is associated with NIDDM was differentially distributed in the 2 cohorts. We discuss the mutations identified, emphasise the importance of the K-ATP channel in physiological processes and discuss the possibility that the disease is caused by mutations in other genes associated with insulin release, glucose metabolism in the β cell or β cell apoptosis and survival. We propose that these processes must be explored in order to further our understanding of PHHI.
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Shah, J., Maguire, D., Brown, D., Cotterill, A. (2008). The Role of ATP Sensitive Channels in Insulin Secretion and The Implications in Persistent Hyperinsulinemic Hypoglycaemia of Infancy (PHHI). In: Maguire, D.J., Bruley, D.F., Harrison, D.K. (eds) Oxygen Transport to Tissue XXVIII. Advances in Experimental Medicine and Biology, vol 599. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71764-7_18
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DOI: https://doi.org/10.1007/978-0-387-71764-7_18
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