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Science. 2011 Oct 28;334(6055):474. doi: 10.1126/science.1210878. Epub 2011 Oct 6.

An activating mutation of AKT2 and human hypoglycemia.

Author information

1
Clinical and Molecular Genetics Unit, Developmental Endocrinology Research Group, Institute of Child Health, University College London, London WC1N 1EH, UK.

Abstract

Pathological fasting hypoglycemia in humans is usually explained by excessive circulating insulin or insulin-like molecules or by inborn errors of metabolism impairing liver glucose production. We studied three unrelated children with unexplained, recurrent, and severe fasting hypoglycemia and asymmetrical growth. All were found to carry the same de novo mutation, p.Glu17Lys, in the serine/threonine kinase AKT2, in two cases as heterozygotes and in one case in mosaic form. In heterologous cells, the mutant AKT2 was constitutively recruited to the plasma membrane, leading to insulin-independent activation of downstream signaling. Thus, systemic metabolic disease can result from constitutive, cell-autonomous activation of signaling pathways normally controlled by insulin.

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PMID:
21979934
PMCID:
PMC3204221
DOI:
10.1126/science.1210878
[Indexed for MEDLINE]
Free PMC Article

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