Metabolic Syndrome Research Center, Diabetes Center, Institute of Metabolism and Endocrinology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Diabetes. 2012 Dec;61(12):3189-98. doi: 10.2337/db12-0249. Epub 2012 Aug 24.
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.
胰岛素分泌缺陷和β细胞数量减少与人类 2 型糖尿病有关，了解这些功能障碍的基础可能揭示糖尿病治疗的策略。在这项研究中，我们表明，在胰腺和胰岛中高度表达的生长因子受体结合蛋白 10 (Grb10) 的胰腺特异性敲除导致胰岛中胰岛素/IGF-1 信号转导升高，β细胞数量和胰岛素含量增加，以及胰岛素分泌增加在小鼠中。胰腺特异性破坏 Grb10 的表达也改善了高脂肪饮食喂养的小鼠的葡萄糖耐量，并保护小鼠免受链脲佐菌素诱导的β细胞凋亡和体重减轻。我们的研究确定 Grb10 是β细胞增殖的重要调节剂，并表明降低 Grb10 的表达水平可能提供一种增加β细胞数量和减少β细胞凋亡的新方法。这对于 1 型和 2 型糖尿病的有效治疗至关重要。
