Pancreatic ß cell proliferation, survival and function are key elements that need to be considered in developing novel antidiabetic therapies. We recently identified CCN5/WISP2 to have potential growth promoting properties when overexpressed in ß cells; however, further investigations are needed to validate those properties. In this study, we demonstrated that exogenous treatment of insulinoma cells and primary islets with recombinant CCN5 (rh-CCN5) protein enhanced the proliferative capacity which was correlated with activation of cell-cycle regulators CDK4 and cyclin D1. Furthermore, pre-incubation of these cells with rh-CCN5 enhanced their survival rate after being exposed to harsh treatments such as streptozotocin and high concentrations of glucose and free fatty acids. CCN5 as well caused an upregulation in the expression of key genes associated with ß cell identity and function such as GLUT-2 and GCK. Finally, CCN5 activated FAK and downstream ERK kinases which are known to stimulate cell proliferation and survival. Hence, our results validate the growth promoting activities of rh-CCN5 in ß cells and open the door for further investigations in vivo.

中文翻译：

---

重组蛋白CCN5 / WISP2在体外促进胰岛细胞增殖和存活。

胰腺β细胞的增殖，存活和功能是开发新型抗糖尿病治疗方法中需要考虑的关键因素。我们最近发现，当在ß细胞中过表达时，CCN5 / WISP2具有潜在的促进生长的特性。但是，需要进一步研究以验证这些属性。在这项研究中，我们证明了用重组CCN5（rh-CCN5）蛋白对胰岛素瘤细胞和原发胰岛进行外源治疗可增强其增殖能力，这与细胞周期调节因子CDK4和细胞周期蛋白D1的激活有关。此外，将这些细胞与rh-CCN5进行预温育可在暴露于苛刻的治疗（如链脲佐菌素和高浓度的葡萄糖和游离脂肪酸）后提高其存活率。CCN5也会引起与ß细胞身份和功能相关的关键基因（例如GLUT-2和GCK）的表达上调。最后，CCN5激活了已知能刺激细胞增殖和存活的FAK和下游ERK激酶。因此，我们的结果验证了rh-CCN5在ß细胞中的生长促进活性，并为进一步体内研究打开了大门。