title: Disruption of growth factor receptor-binding protein 10 in the pancreas enhances β-cell proliferation and protects mice from streptozotocin-induced β-cell apoptosis.
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.
authors.affiliation: Metabolic Syndrome Research Center, Diabetes Center, Institute of Metabolism and Endocrinology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Meilian
authors.initials: M
authors.lastname: Liu
authors.forename: Xiuling
authors.initials: X
authors.lastname: Li
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.forename: John M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D051383:GRB10 Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000378:metabolism*; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D051383:GRB10 Adaptor Protein; D013311:Streptozocin