Visualising replication and neogenesis of rodent and human pancreatic islets

啮齿动物和人类胰岛复制和新生的可视化

• 批准号: 126893320
• 负责人: Professor Dr. Stephan Speier
• 金额: --
• 依托单位: Institut für Physiologie
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/126893320?language=en
• 关键词: Visualising; replication; neogenesis; rodent; human

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.

糖尿病伴随着严重的并发症和高死亡率。这是由于体内唯一的胰岛素来源--功能性胰岛β细胞丧失后，血糖浓度升高，胰岛素释放不足所致。尽管医学研究取得了进展，但仍然没有治愈的迹象，目前可用的大多数治疗方法也不能使患者过上正常的生活。再生胰岛素分泌的β细胞是开发治疗靶点的一种很有前途的新方法。因此，人体通过新生的祖细胞或通过复制从先前存在的β细胞再生新的功能细胞的能力被用来取代丢失的细胞。其目的要么是在体内增加患者体内的功能β细胞的质量，要么是在体外将其移植到患者体内之前。到目前为止，对导致β细胞新生或复制的信号和机制的了解相当有限。这在一定程度上是因为对啮齿动物的研究，特别是对自然环境中的人类β细胞的研究，即在体内，缺乏研究。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活体成像平台来实现这一点，该平台能够在细胞分辨率下对β细胞生物学进行纵向研究。

项目成果

Alterations in β-Cell Calcium Dynamics and Efficacy Outweigh Islet Mass Adaptation in Compensation of Insulin Resistance and Prediabetes Onset

• DOI: 10.2337/db15-1718
• 发表时间: 2016-09-01
• 期刊: DIABETES
• 影响因子: 7.7
• 作者: Chen, Chunguang;Chmelova, Helena;Speier, Stephan
• 通讯作者: Speier, Stephan

Distinct Roles of β-Cell Mass and Function During Type 1 Diabetes Onset and Remission

• DOI: 10.2337/db14-1055
• 发表时间: 2015-06-01
• 期刊: DIABETES
• 影响因子: 7.7
• 作者: Chmelova, Helena;Cohrs, Christian M.;Speier, Stephan
• 通讯作者: Speier, Stephan

Vessel Network Architecture of Adult Human Islets Promotes Distinct Cell-Cell Interactions In Situ and Is Altered After Transplantation

• DOI: 10.1210/en.2016-1184
• 发表时间: 2017-05-01
• 期刊: ENDOCRINOLOGY
• 影响因子: 4.8
• 作者: Cohrs, Christian M.;Chen, Chunguang;Speier, Stephan
• 通讯作者: Speier, Stephan

The biomechanical properties of an epithelial tissue determine the location of its vasculature

上皮组织的生物力学特性决定其脉管系统的位置

• DOI: 10.1038/ncomms13560
• 发表时间: 2016
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: Schubert;Karsjens;Bartosinska;Eberhard;Jeruschke;Alsteens;Speier;Müller;Lammert
• 通讯作者: Lammert

Identification of proliferative and mature β-cells in the islets of Langerhans

• DOI: 10.1038/nature18624
• 发表时间: 2016-07-21
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Bader, Erik;Migliorini, Adriana;Lickert, Heiko
• 通讯作者: Lickert, Heiko