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Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a

Expanding β-cell mass through β-cell proliferation is considered a potential therapeutic approach to treat β-cell failure in diabetic patients. A necessary step toward achieving this goal is to identify signaling pathways that regulate β-cell proliferation in vivo. Here we show that osteocalcin, a b...

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Detalles Bibliográficos
Autores principales: Wei, Jianwen, Hanna, Timothy, Suda, Nina, Karsenty, Gerard, Ducy, Patricia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931403/
https://www.ncbi.nlm.nih.gov/pubmed/24009262
http://dx.doi.org/10.2337/db13-0887
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author Wei, Jianwen
Hanna, Timothy
Suda, Nina
Karsenty, Gerard
Ducy, Patricia
author_facet Wei, Jianwen
Hanna, Timothy
Suda, Nina
Karsenty, Gerard
Ducy, Patricia
author_sort Wei, Jianwen
collection PubMed
description Expanding β-cell mass through β-cell proliferation is considered a potential therapeutic approach to treat β-cell failure in diabetic patients. A necessary step toward achieving this goal is to identify signaling pathways that regulate β-cell proliferation in vivo. Here we show that osteocalcin, a bone-derived hormone, regulates β-cell replication in a cyclin D1–dependent manner by signaling through the Gprc6a receptor expressed in these cells. Accordingly, mice lacking Gprc6a in the β-cell lineage only are glucose intolerant due to an impaired ability to produce insulin. Remarkably, this regulation occurs during both the perinatal peak of β-cell proliferation and in adulthood. Hence, the loss of osteocalcin/Gprc6a signaling has a profound effect on β-cell mass accrual during late pancreas morphogenesis. This study extends the endocrine role of osteocalcin to the developmental period and establishes osteocalcin/Gprc6a signaling as a major regulator of β-cell endowment that can become a potential target for β-cell proliferative therapies.
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spelling pubmed-39314032015-03-01 Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a Wei, Jianwen Hanna, Timothy Suda, Nina Karsenty, Gerard Ducy, Patricia Diabetes Islet Studies Expanding β-cell mass through β-cell proliferation is considered a potential therapeutic approach to treat β-cell failure in diabetic patients. A necessary step toward achieving this goal is to identify signaling pathways that regulate β-cell proliferation in vivo. Here we show that osteocalcin, a bone-derived hormone, regulates β-cell replication in a cyclin D1–dependent manner by signaling through the Gprc6a receptor expressed in these cells. Accordingly, mice lacking Gprc6a in the β-cell lineage only are glucose intolerant due to an impaired ability to produce insulin. Remarkably, this regulation occurs during both the perinatal peak of β-cell proliferation and in adulthood. Hence, the loss of osteocalcin/Gprc6a signaling has a profound effect on β-cell mass accrual during late pancreas morphogenesis. This study extends the endocrine role of osteocalcin to the developmental period and establishes osteocalcin/Gprc6a signaling as a major regulator of β-cell endowment that can become a potential target for β-cell proliferative therapies. American Diabetes Association 2014-03 2014-02-13 /pmc/articles/PMC3931403/ /pubmed/24009262 http://dx.doi.org/10.2337/db13-0887 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Islet Studies
Wei, Jianwen
Hanna, Timothy
Suda, Nina
Karsenty, Gerard
Ducy, Patricia
Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a
title Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a
title_full Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a
title_fullStr Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a
title_full_unstemmed Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a
title_short Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a
title_sort osteocalcin promotes β-cell proliferation during development and adulthood through gprc6a
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931403/
https://www.ncbi.nlm.nih.gov/pubmed/24009262
http://dx.doi.org/10.2337/db13-0887
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