Expanding the mass of pancreatic insulin-producing beta cells through re-activation of beta cell replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Pancreatic beta cells exhibit an age-dependent decrease in their proliferative activity, partly related to changes in the systemic environment. Here we report the identification of CCN4/Wisp1 as a circulating factor more abundant in pre-weaning than in adult mice. We show that Wisp1 promotes endogenous and transplanted adult beta cell proliferation in vivo. We validate these findings using isolated mouse and human islets and find that the beta cell trophic effect of Wisp1 is dependent on Akt signaling. In summary, our study reveals the role of Wisp1 as an inducer of beta cell replication, supporting the idea that the use of young blood factors may be a useful strategy to expand adult beta cell mass.

已经提出通过重新激活β细胞复制来扩大产生胰腺胰岛素的β细胞的质量，作为预防或延迟糖尿病出现的疗法。胰腺β细胞的增殖活性随年龄而下降，部分与全身环境的变化有关。在这里，我们报告CCN4 / Wisp1作为循环因子在断奶前比成年小鼠中丰富的鉴定。我们显示Wisp1体内促进内源性和移植的成年β细胞增殖。我们使用隔离的小鼠和人类胰岛验证了这些发现，并发现Wisp1的β细胞营养作用取决于Akt信号传导。总而言之，我们的研究揭示了Wisp1作为β细胞复制的诱导剂的作用，