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Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes

The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels...

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Autores principales: Huesa, Carmen, Zhu, Dongxing, Glover, James D., Ferron, Mathieu, Karsenty, Gerard, Milne, Elspeth M., Millan, José Luis, Ahmed, S. Faisal, Farquharson, Colin, Morton, Nicholas M., MacRae, Vicky E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Limited 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257003/
https://www.ncbi.nlm.nih.gov/pubmed/25368121
http://dx.doi.org/10.1242/dmm.017905
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author Huesa, Carmen
Zhu, Dongxing
Glover, James D.
Ferron, Mathieu
Karsenty, Gerard
Milne, Elspeth M.
Millan, José Luis
Ahmed, S. Faisal
Farquharson, Colin
Morton, Nicholas M.
MacRae, Vicky E.
author_facet Huesa, Carmen
Zhu, Dongxing
Glover, James D.
Ferron, Mathieu
Karsenty, Gerard
Milne, Elspeth M.
Millan, José Luis
Ahmed, S. Faisal
Farquharson, Colin
Morton, Nicholas M.
MacRae, Vicky E.
author_sort Huesa, Carmen
collection PubMed
description The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels of NPP1 are elevated both in dermal fibroblast cultures and muscle of individuals with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the gene that encodes NPP1 (Enpp1(−/−) mice). Enpp1(−/−) mice exhibited mildly improved glucose homeostasis on a normal diet but showed a pronounced resistance to obesity and insulin resistance in response to chronic high-fat feeding. Enpp1(−/−) mice had increased levels of the insulin-sensitizing bone-derived hormone osteocalcin but unchanged insulin signalling within osteoblasts. A fuller understanding of the pathways of NPP1 could inform the development of novel therapeutic strategies for treating insulin resistance.
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spelling pubmed-42570032014-12-12 Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes Huesa, Carmen Zhu, Dongxing Glover, James D. Ferron, Mathieu Karsenty, Gerard Milne, Elspeth M. Millan, José Luis Ahmed, S. Faisal Farquharson, Colin Morton, Nicholas M. MacRae, Vicky E. Dis Model Mech Research Article The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels of NPP1 are elevated both in dermal fibroblast cultures and muscle of individuals with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the gene that encodes NPP1 (Enpp1(−/−) mice). Enpp1(−/−) mice exhibited mildly improved glucose homeostasis on a normal diet but showed a pronounced resistance to obesity and insulin resistance in response to chronic high-fat feeding. Enpp1(−/−) mice had increased levels of the insulin-sensitizing bone-derived hormone osteocalcin but unchanged insulin signalling within osteoblasts. A fuller understanding of the pathways of NPP1 could inform the development of novel therapeutic strategies for treating insulin resistance. The Company of Biologists Limited 2014-12 2014-10-31 /pmc/articles/PMC4257003/ /pubmed/25368121 http://dx.doi.org/10.1242/dmm.017905 Text en © 2014. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Huesa, Carmen
Zhu, Dongxing
Glover, James D.
Ferron, Mathieu
Karsenty, Gerard
Milne, Elspeth M.
Millan, José Luis
Ahmed, S. Faisal
Farquharson, Colin
Morton, Nicholas M.
MacRae, Vicky E.
Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes
title Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes
title_full Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes
title_fullStr Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes
title_full_unstemmed Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes
title_short Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes
title_sort deficiency of the bone mineralization inhibitor npp1 protects mice against obesity and diabetes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257003/
https://www.ncbi.nlm.nih.gov/pubmed/25368121
http://dx.doi.org/10.1242/dmm.017905
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