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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...

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Autores principales: Xiao, Xiangwei, Wiersch, John, El-Gohary, Yousef, Guo, Ping, Prasadan, Krishna, Paredes, Jose, Welsh, Carey, Shiota, Chiyo, Gittes, George K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
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.
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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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