Investigation of Ephrin-A Reverse Signaling in Pancreatic Islets

胰岛中 Ephrin-A 反向信号传导的研究

• 批准号: 61027617
• 负责人: Professor Dr. Eckhard Lammert
• 金额: --
• 依托单位: Institut für Stoffwechselphysiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/61027617?language=en
• 关键词: Investigation; Ephrin; Reverse; Signaling; Pancreatic

We have shown that beta cells in the mouse and human pancreas strongly express ephrin-A1 and ephrin-A5. Ephrin-A5-deficient mice have a defective glucose tolerance and decreased glucose-stimulated insulin secretion, showing that ephrin-A5 is required for normal insulin secretion. Conversely, activation of ephrin-A reverse signaling via EphA5-Fc fusion proteins strongly increases insulin secretion from mouse and human pancreatic islets as well as mouse insulinoma cells (MIN6). Our results therefore suggest that ephrin-A reverse signaling may play a role in diabetes and might be useful for diabetes treatment in humans. To continue this project, we would like to identify and characterize the components of this signaling pathway in pancreatic beta cells. We want to understand the role of ephrin-A1 in insulin secretion as well as uncover the mechanisms by which ephrin-As stimulate insulin secretion.

我们已经证明，小鼠和人类胰腺中的β细胞强烈表达eaffin-A1和eaffin-A5。肾上腺素-A5基因缺陷的小鼠存在糖耐量缺陷，葡萄糖刺激的胰岛素分泌减少，这表明正常的胰岛素分泌需要肾上腺素-A5。反之，通过EPHA5-Fc融合蛋白激活eaffin-A反向信号会强烈增加小鼠和人胰岛以及小鼠胰岛素瘤细胞(MIN6)的胰岛素分泌。因此，我们的研究结果表明，肾上腺素-A反向信号可能在糖尿病中发挥作用，并可能对人类的糖尿病治疗有用。为了继续这个项目，我们想要识别和表征胰岛β细胞中这一信号通路的组成部分。我们希望了解eaffin-A1在胰岛素分泌中的作用，并揭示eaffin-A刺激胰岛素分泌的机制。