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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2014
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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. |
format | Online Article Text |
id | pubmed-3931403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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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