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

描述（由申请人提供）：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与β细胞功能和存活率降低有关。我们的实验室最近表明，胰岛素本身控制着β细胞的存活。研究目的：拟议研究的目标是表征胰岛素调节人类和小鼠胰岛中β细胞存活的机制。我们假设胰岛素可能通过一种称为Raf-1的激酶促进β细胞存活。研究项目描述：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β细胞胰岛素信号传导中的作用。与糖尿病的相关性：我们希望我们提出的实验能够产生关于胰岛素作为β细胞存活因子的新机制信息。更好地了解人类胰岛细胞凋亡的控制对于预防所有类型糖尿病中的β细胞死亡和改善临床胰岛移植至关重要。

DESCRIPTION (provided by applicant): 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.