Disruption of growth factor receptor-binding protein 10 in the pancreas enhances β-cell proliferation and protects mice from streptozotocin-induced b-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 journalArticlepeer-review

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
JournalVeterinary Record
Volume174
Issue number19
StatePublished - May 10 2014

ASJC Scopus subject areas

  • veterinary(all)

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