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TGFβ Receptor Signaling Is Essential for Inflammation-Induced but Not β-Cell Workload–Induced β-Cell Proliferation
Protection and restoration of a functional β-cell mass are fundamental strategies for prevention and treatment of diabetes. Consequently, knowledge of signals that determine the functional β-cell mass is of immense clinical relevance. Transforming growth factor β (TGFβ) superfamily signaling pathway...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609557/ https://www.ncbi.nlm.nih.gov/pubmed/23248173 http://dx.doi.org/10.2337/db12-1428 |
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author | Xiao, Xiangwei Wiersch, John El-Gohary, Yousef Guo, Ping Prasadan, Krishna Paredes, Jose Welsh, Carey Shiota, Chiyo Gittes, George K. |
author_facet | Xiao, Xiangwei Wiersch, John El-Gohary, Yousef Guo, Ping Prasadan, Krishna Paredes, Jose Welsh, Carey Shiota, Chiyo Gittes, George K. |
author_sort | Xiao, Xiangwei |
collection | PubMed |
description | Protection and restoration of a functional β-cell mass are fundamental strategies for prevention and treatment of diabetes. Consequently, knowledge of signals that determine the functional β-cell mass is of immense clinical relevance. Transforming growth factor β (TGFβ) superfamily signaling pathways play a critical role in development and tissue specification. Nevertheless, the role of these pathways in adult β-cell homeostasis is not well defined. Here, we ablated TGFβ receptor I and II genes in mice undergoing two surgical β-cell replication models (partial pancreatectomy or partial duct ligation), representing two triggers for β-cell proliferation, increased β-cell workload and local inflammation, respectively. Our data suggest that TGFβ receptor signaling is necessary for baseline β-cell proliferation. By either provision of excess glucose or treatment with exogenous insulin, we further demonstrated that inflammation and increased β-cell workload are both stimulants for β-cell proliferation but are TGFβ receptor signaling dependent and independent, respectively. Collectively, by using a pancreas-specific TGFβ receptor–deleted mouse model, we have identified two distinct pathways that regulate adult β-cell proliferation. Our study thus provides important information for understanding β-cell proliferation during normal growth and in pancreatic diseases. |
format | Online Article Text |
id | pubmed-3609557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-36095572014-04-01 TGFβ Receptor Signaling Is Essential for Inflammation-Induced but Not β-Cell Workload–Induced β-Cell Proliferation Xiao, Xiangwei Wiersch, John El-Gohary, Yousef Guo, Ping Prasadan, Krishna Paredes, Jose Welsh, Carey Shiota, Chiyo Gittes, George K. Diabetes Original Research Protection and restoration of a functional β-cell mass are fundamental strategies for prevention and treatment of diabetes. Consequently, knowledge of signals that determine the functional β-cell mass is of immense clinical relevance. Transforming growth factor β (TGFβ) superfamily signaling pathways play a critical role in development and tissue specification. Nevertheless, the role of these pathways in adult β-cell homeostasis is not well defined. Here, we ablated TGFβ receptor I and II genes in mice undergoing two surgical β-cell replication models (partial pancreatectomy or partial duct ligation), representing two triggers for β-cell proliferation, increased β-cell workload and local inflammation, respectively. Our data suggest that TGFβ receptor signaling is necessary for baseline β-cell proliferation. By either provision of excess glucose or treatment with exogenous insulin, we further demonstrated that inflammation and increased β-cell workload are both stimulants for β-cell proliferation but are TGFβ receptor signaling dependent and independent, respectively. Collectively, by using a pancreas-specific TGFβ receptor–deleted mouse model, we have identified two distinct pathways that regulate adult β-cell proliferation. Our study thus provides important information for understanding β-cell proliferation during normal growth and in pancreatic diseases. American Diabetes Association 2013-04 2013-03-14 /pmc/articles/PMC3609557/ /pubmed/23248173 http://dx.doi.org/10.2337/db12-1428 Text en © 2013 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 | Original Research Xiao, Xiangwei Wiersch, John El-Gohary, Yousef Guo, Ping Prasadan, Krishna Paredes, Jose Welsh, Carey Shiota, Chiyo Gittes, George K. TGFβ Receptor Signaling Is Essential for Inflammation-Induced but Not β-Cell Workload–Induced β-Cell Proliferation |
title | TGFβ Receptor Signaling Is Essential for Inflammation-Induced but Not β-Cell Workload–Induced β-Cell Proliferation |
title_full | TGFβ Receptor Signaling Is Essential for Inflammation-Induced but Not β-Cell Workload–Induced β-Cell Proliferation |
title_fullStr | TGFβ Receptor Signaling Is Essential for Inflammation-Induced but Not β-Cell Workload–Induced β-Cell Proliferation |
title_full_unstemmed | TGFβ Receptor Signaling Is Essential for Inflammation-Induced but Not β-Cell Workload–Induced β-Cell Proliferation |
title_short | TGFβ Receptor Signaling Is Essential for Inflammation-Induced but Not β-Cell Workload–Induced β-Cell Proliferation |
title_sort | tgfβ receptor signaling is essential for inflammation-induced but not β-cell workload–induced β-cell proliferation |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609557/ https://www.ncbi.nlm.nih.gov/pubmed/23248173 http://dx.doi.org/10.2337/db12-1428 |
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