Anti-apoptotic role of raf-1 in beta-cell insulin signaling

背景：糖尿病是美国的一个主要健康问题。尽管进行了广泛的研究，但 这种疾病的确切原因尚不清楚。然而，有证据表明，所有形式的糖尿病都是 与降低的β细胞功能和存活率有关。我们的实验室最近证明了胰岛素本身 控制着β细胞的存活。 研究目标：拟议研究的目标是描述 胰岛素调节人和小鼠胰岛中的β细胞存活。我们假设胰岛素可能促进 β细胞通过一种名为Raf-1的激酶存活。 研究项目简介：我们将利用分子生物学、活细胞成像和基因敲除小鼠来 剖析Raf-1在抗凋亡的β细胞胰岛素信号转导中的作用。 与糖尿病的相关性：我们希望我们提议的实验能产生新的机制信息 认为胰岛素是一种β细胞生存因素。更好地理解人类对细胞凋亡的控制 胰岛对于预防所有类型糖尿病的胰岛细胞死亡和改善临床胰岛移植是至关重要的。

Background: Diabetes is a major health problem in United States of America. Despite extensive study, the exact causes of this disease are not known. However, evidence suggests that all forms of diabetes are associated with reduced beta-cell function and survival. Our laboratory has recently shown that insulin itself controls beta-cell survival. Objective of research: The goal of the proposed research is to characterize the mechanisms through which insulin regulates beta-cell survival in human and mouse islets. We hypothesize that insulin may promote beta-cell survival via a kinase called Raf-1. Description of research project: We will utilize molecular biology, live-cell imaging and knockout mice to dissect the role of Raf-1 in anti-apoptotic beta-cell insulin signaling. Relevancy to diabetes: We expect our proposed experiments to yield new mechanistic information regarding insulin as a beta-cell survival factor. Greater understanding of the control of apoptosis in human islets is crucial to prevent beta-cell death in all types of diabetes and to improve clinical islet transplantation.