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 Zhang, Ning Zhang, Meilian Liu, Xiuling Li, Lijun Zhou, Wei Huang, Zhipeng Xu, Jing Liu, Nicolas Musi, Ralph A. DeFronzo, John M. Cunningham, Zhiguang Zhou, Xin Yun Lu, Feng Liu

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3189-3198
Number of pages10
JournalDiabetes
Volume61
Issue number12
DOIs
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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