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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

Authors :
Meilian Liu
Zhiguang Zhou
Ralph A. DeFronzo
Xin Yun Lu
Jingjing Zhang
Lijun Zhou
Ning Zhang
Xiuling Li
John M. Cunningham
Wei Huang
Nicolas Musi
Jing Liu
Feng Liu
Zhipeng Xu
Source :
Diabetes. 61:3189-3198
Publication Year :
2012
Publisher :
American Diabetes Association, 2012.

Abstract

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.

Details

ISSN :
1939327X and 00121797
Volume :
61
Database :
OpenAIRE
Journal :
Diabetes
Accession number :
edsair.doi...........f30e2a4b1c502df63325edb8990be185
Full Text :
https://doi.org/10.2337/db12-0249