Visualising replication and neogenesis of rodent and human pancreatic islets

糖尿病伴随严重的并发症和高死亡率。这是由于功能性胰腺β细胞（体内胰岛素的唯一来源）丧失后，响应于血糖浓度升高而释放的胰岛素不足。尽管医学研究取得了进展，但仍然没有治愈的希望，目前可用的大多数治疗方法不能使患者过上正常的生活。胰岛素分泌β细胞的再生是开发治疗靶点的有希望的新方法。因此，身体通过新生从祖细胞或通过复制从预先存在的β细胞再生新功能细胞的能力被用于替换丢失的细胞。其目的是在体内或体外实验室中增加患者体内功能性β细胞的质量。迄今为止，导致β细胞新生或复制的信号和机制的知识非常有限。这部分是因为缺少对啮齿动物，特别是对自然环境中（即体内）人类β细胞的研究。该项目的目的是评估在体内不同刺激条件下复制和新生对β细胞再生的贡献。此外，我们将研究特定的调节分子在导致复制的信号通路中的作用。我们将使用一种新的体内成像平台来实现这一目标，该平台能够以细胞分辨率对β细胞生物学进行纵向研究。

Diabetes mellitus is associated with severe complications and high mortality. This is the due to insufficient release of insulin in response to increased blood glucose concentrations after loss of functional pancreatic beta-cells, the sole source of insulin in the body. Despite the progress in medical research there is still no cure in sight and most currently available treatments do not enable patients to lead a normal life.Regeneration of insulin secreting beta-cells is a promising new approach towards the development of therapeutic targets. Hereby, the body’s ability to regenerate new functional cells from progenitor cells by neogenesis or from pre-existing beta-cells by replication is being used to replace the lost cells. The aim is to either increase the mass of functional beta-cells inside the patient’s body in vivo or before transplantation to a patient in the laboratory in vitro.So far knowledge of the signals and mechanisms leading to neogenesis or replication of beta-cells is quite limited. This is partially because studies on rodent but especially on human beta-cells in a natural environment, i.e. in vivo, are missing. The aim of this project is to evaluate the contribution of replication and neogenesis to beta-cell regeneration under diverse stimulatory conditions in vivo. Furthermore, we will investigate the role of specific regulatory molecules in the signaling pathways leading to replication. This we will be achieved using a novel in vivo imaging platform which enables longitudinal studies of beta-cell biology at cellular resolution.