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

21 Citations (Scopus)

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 2012

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Growth Factor Receptors
Streptozocin
Pancreas
Carrier Proteins
Cell Proliferation
Insulin
Apoptosis
Type 2 Diabetes Mellitus
High Fat Diet
Type 1 Diabetes Mellitus
Insulin-Like Growth Factor I
Islets of Langerhans
Weight Loss
Body Weight
Glucose
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Disruption of growth factor receptor-binding protein 10 in the pancreas enhances β-cell proliferation and protects mice from streptozotocin-induced β-cell apoptosis. / Zhang, Jingjing; Zhang, Ning; Liu, Meilian; Li, Xiuling; Zhou, Lijun; Huang, Wei; Xu, Zhipeng; Liu, Jing; Musi, Nicolas; Defronzo, Ralph A; Cunningham, John M.; Zhou, Zhiguang; Lu, Xin Yun; Liu, Feng.

In: Diabetes, Vol. 61, No. 12, 12.2012, p. 3189-3198.

Research output: Contribution to journalArticle

Zhang, Jingjing ; Zhang, Ning ; Liu, Meilian ; Li, Xiuling ; Zhou, Lijun ; Huang, Wei ; Xu, Zhipeng ; Liu, Jing ; Musi, Nicolas ; Defronzo, Ralph A ; Cunningham, John M. ; Zhou, Zhiguang ; Lu, Xin Yun ; Liu, Feng. / Disruption of growth factor receptor-binding protein 10 in the pancreas enhances β-cell proliferation and protects mice from streptozotocin-induced β-cell apoptosis. In: Diabetes. 2012 ; Vol. 61, No. 12. pp. 3189-3198.
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