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

  1. Feng Liu1,2
  1. 1From the Metabolic Syndrome Research Center, Diabetes Center, Institute of Metabolism and Endocrinology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China; the
  2. 2Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas; the
  3. 3Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; the
  4. 4Department of Hematology/Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee; and the
  5. 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
  1. Corresponding author: Feng Liu, liuf{at}uthscsa.edu.

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.

Footnotes

  • Received February 27, 2012.
  • Accepted June 26, 2012.

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  1. Diabetes vol. 61 no. 12 3189-3198
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