Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis
- Jingjing Zhang1,2,
- Ning Zhang3,
- Meilian Liu2,
- Xiuling Li4,
- Lijun Zhou2,
- Wei Huang1,
- Zhipeng Xu1,
- Jing Liu2,
- Nicolas Musi3,
- Ralph A. DeFronzo3,
- John M. Cunningham4,
- Zhiguang Zhou1,5,
- Xin-Yun Lu2 and
- Feng Liu1,2⇓
- 1From the Metabolic Syndrome Research Center, Diabetes Center, Institute of Metabolism and Endocrinology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China; the
- 2Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas; the
- 3Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; the
- 4Department of Hematology/Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee; and the
- 5Key Laboratory of Diabetes Immunology, Ministry of Education, Diabetes Center, Institute of Metabolism and Endocrinology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Corresponding author: Feng Liu, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0249/-/DC1.
See accompanying commentary, p. 3066.
- Received February 27, 2012.
- Accepted June 26, 2012.
- © 2012 by the American Diabetes Association.
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