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Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis

Defects in insulin secretion and reduction in β-cell mass are associated with type 2 diabetes in humans, and understanding the basis for these dysfunctions may reveal strategies for diabetes therapy. In this study, we show that pancreas-specific knockout of growth factor receptor–binding protein 10...

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Autores principales: Zhang, Jingjing, Zhang, Ning, Liu, Meilian, Li, Xiuling, Zhou, Lijun, Huang, Wei, Xu, Zhipeng, Liu, Jing, Musi, Nicolas, DeFronzo, Ralph A., Cunningham, John M., Zhou, Zhiguang, Lu, Xin-Yun, Liu, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501856/
https://www.ncbi.nlm.nih.gov/pubmed/22923474
http://dx.doi.org/10.2337/db12-0249
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author Zhang, Jingjing
Zhang, Ning
Liu, Meilian
Li, Xiuling
Zhou, Lijun
Huang, Wei
Xu, Zhipeng
Liu, Jing
Musi, Nicolas
DeFronzo, Ralph A.
Cunningham, John M.
Zhou, Zhiguang
Lu, Xin-Yun
Liu, Feng
author_facet Zhang, Jingjing
Zhang, Ning
Liu, Meilian
Li, Xiuling
Zhou, Lijun
Huang, Wei
Xu, Zhipeng
Liu, Jing
Musi, Nicolas
DeFronzo, Ralph A.
Cunningham, John M.
Zhou, Zhiguang
Lu, Xin-Yun
Liu, Feng
author_sort Zhang, Jingjing
collection PubMed
description Defects in insulin secretion and reduction in β-cell mass are associated with type 2 diabetes in humans, and understanding the basis for these dysfunctions may reveal strategies for diabetes therapy. In this study, we show that pancreas-specific knockout of growth factor receptor–binding protein 10 (Grb10), which is highly expressed in pancreas and islets, leads to elevated insulin/IGF-1 signaling in islets, enhanced β-cell mass and insulin content, and increased insulin secretion in mice. Pancreas-specific disruption of Grb10 expression also improved glucose tolerance in mice fed with a high-fat diet and protected mice from streptozotocin-induced β-cell apoptosis and body weight loss. Our study has identified Grb10 as an important regulator of β-cell proliferation and demonstrated that reducing the expression level of Grb10 could provide a novel means to increase β-cell mass and reduce β-cell apoptosis. This is critical for effective therapeutic treatment of both type 1 and 2 diabetes.
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spelling pubmed-35018562013-12-01 Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis Zhang, Jingjing Zhang, Ning Liu, Meilian Li, Xiuling Zhou, Lijun Huang, Wei Xu, Zhipeng Liu, Jing Musi, Nicolas DeFronzo, Ralph A. Cunningham, John M. Zhou, Zhiguang Lu, Xin-Yun Liu, Feng Diabetes Signal Transduction Defects in insulin secretion and reduction in β-cell mass are associated with type 2 diabetes in humans, and understanding the basis for these dysfunctions may reveal strategies for diabetes therapy. In this study, we show that pancreas-specific knockout of growth factor receptor–binding protein 10 (Grb10), which is highly expressed in pancreas and islets, leads to elevated insulin/IGF-1 signaling in islets, enhanced β-cell mass and insulin content, and increased insulin secretion in mice. Pancreas-specific disruption of Grb10 expression also improved glucose tolerance in mice fed with a high-fat diet and protected mice from streptozotocin-induced β-cell apoptosis and body weight loss. Our study has identified Grb10 as an important regulator of β-cell proliferation and demonstrated that reducing the expression level of Grb10 could provide a novel means to increase β-cell mass and reduce β-cell apoptosis. This is critical for effective therapeutic treatment of both type 1 and 2 diabetes. American Diabetes Association 2012-12 2012-11-15 /pmc/articles/PMC3501856/ /pubmed/22923474 http://dx.doi.org/10.2337/db12-0249 Text en © 2012 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 Signal Transduction
Zhang, Jingjing
Zhang, Ning
Liu, Meilian
Li, Xiuling
Zhou, Lijun
Huang, Wei
Xu, Zhipeng
Liu, Jing
Musi, Nicolas
DeFronzo, Ralph A.
Cunningham, John M.
Zhou, Zhiguang
Lu, Xin-Yun
Liu, Feng
Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis
title Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis
title_full Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis
title_fullStr Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis
title_full_unstemmed Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis
title_short Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis
title_sort disruption of growth factor receptor–binding protein 10 in the pancreas enhances β-cell proliferation and protects mice from streptozotocin-induced β-cell apoptosis
topic Signal Transduction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501856/
https://www.ncbi.nlm.nih.gov/pubmed/22923474
http://dx.doi.org/10.2337/db12-0249
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