Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.

Although the most common mechanism underlying congenital hyperinsulinism is dysfunction of the pancreatic ATP-sensitive potassium channel, the pathogenesis and genetic origins of this disease remains largely unexplained in more than half of all patients. UCP2 knockout mice exhibit an hyperinsulinemi...

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Autores principales:	M Mar González-Barroso, Irina Giurgea, Fredéric Bouillaud, Andrea Anedda, Christine Bellanné-Chantelot, Laurence Hubert, Yves de Keyzer, Pascale de Lonlay, Daniel Ricquier
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d46ac5c1e6e4f8aa527d7b2e5f7cdd6
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spelling	oai:doaj.org-article:1d46ac5c1e6e4f8aa527d7b2e5f7cdd62021-11-25T06:18:15ZMutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.1932-620310.1371/journal.pone.0003850https://doaj.org/article/1d46ac5c1e6e4f8aa527d7b2e5f7cdd62008-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19065272/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Although the most common mechanism underlying congenital hyperinsulinism is dysfunction of the pancreatic ATP-sensitive potassium channel, the pathogenesis and genetic origins of this disease remains largely unexplained in more than half of all patients. UCP2 knockout mice exhibit an hyperinsulinemic hypoglycemia, suggesting an involvement of UCP2 in insulin secretion. However, a possible pathogenic role for UCP2 protein in the development of human congenital hyperinsulinism or of any human disease has not yet been investigated. We studied ten children exhibiting congenital hyperinsulinism, without detectable mutations in the known congenital hyperinsulinism-causing genes. Parental-inherited heterozygous UCP2 variants encoding amino-acid changes were found in two unrelated children with congenital hyperinsulinism. Functional assays in yeast and in insulin-secreting cells revealed an impaired activity of UCP2 mutants. Therefore, we report the finding of UCP2 coding variants in human congenital hyperinsulinism, which reveals a role for this gene in the regulation of insulin secretion and glucose metabolism in humans. Our results show for the first time a direct association between UCP2 amino acid alteration and human disease and highlight a role for mitochondria in hormone secretion.M Mar González-BarrosoIrina GiurgeaFredéric BouillaudAndrea AneddaChristine Bellanné-ChantelotLaurence HubertYves de KeyzerPascale de LonlayDaniel RicquierPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 12, p e3850 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M Mar González-Barroso Irina Giurgea Fredéric Bouillaud Andrea Anedda Christine Bellanné-Chantelot Laurence Hubert Yves de Keyzer Pascale de Lonlay Daniel Ricquier Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.
description	Although the most common mechanism underlying congenital hyperinsulinism is dysfunction of the pancreatic ATP-sensitive potassium channel, the pathogenesis and genetic origins of this disease remains largely unexplained in more than half of all patients. UCP2 knockout mice exhibit an hyperinsulinemic hypoglycemia, suggesting an involvement of UCP2 in insulin secretion. However, a possible pathogenic role for UCP2 protein in the development of human congenital hyperinsulinism or of any human disease has not yet been investigated. We studied ten children exhibiting congenital hyperinsulinism, without detectable mutations in the known congenital hyperinsulinism-causing genes. Parental-inherited heterozygous UCP2 variants encoding amino-acid changes were found in two unrelated children with congenital hyperinsulinism. Functional assays in yeast and in insulin-secreting cells revealed an impaired activity of UCP2 mutants. Therefore, we report the finding of UCP2 coding variants in human congenital hyperinsulinism, which reveals a role for this gene in the regulation of insulin secretion and glucose metabolism in humans. Our results show for the first time a direct association between UCP2 amino acid alteration and human disease and highlight a role for mitochondria in hormone secretion.
format	article
author	M Mar González-Barroso Irina Giurgea Fredéric Bouillaud Andrea Anedda Christine Bellanné-Chantelot Laurence Hubert Yves de Keyzer Pascale de Lonlay Daniel Ricquier
author_facet	M Mar González-Barroso Irina Giurgea Fredéric Bouillaud Andrea Anedda Christine Bellanné-Chantelot Laurence Hubert Yves de Keyzer Pascale de Lonlay Daniel Ricquier
author_sort	M Mar González-Barroso
title	Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.
title_short	Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.
title_full	Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.
title_fullStr	Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.
title_full_unstemmed	Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.
title_sort	mutations in ucp2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/1d46ac5c1e6e4f8aa527d7b2e5f7cdd6
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Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion.

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