COBRE: INSULIN RECEPTOR SIGNALING IN DIABETIC RETINOPATHY

COBRE：糖尿病视网膜病变中的胰岛素受体信号传导

• 批准号: 7610500
• 负责人: Raju VS Rajala
• 金额: $ 7.26万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-05 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610500
• 关键词: Actins; Age; Blindness; Complications of Diabetes Mellitus; Computer Retrieval of Information on Scientific Projects Database; Condition; Deterioration; Diabetes Mellitus; Diabetic Retinopathy; Funding; Grant; Hyperglycemia; Institution; Insulin Receptor; Neural Retina; Pathology; Phosphatidylinositols; Phosphotransferases; Population; Receptor Activation; Receptor Signaling; Reporting; Research; Research Personnel; Resources; Retinal; Source; United States National Institutes of Health; Work; in vivo; neuron apoptosis; novel; retinal neuron

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetic retinopathy is the most common complication of diabetes and the leading cause of vision loss in the working age population. A growing body of evidence suggests that the neural retina undergoes significant deterioration early in the course of diabetes. Insulin receptor (IR) activation has been shown to rescue retinal neurons from apoptosis through a phosphoinositide 3-kinase cascade. Retinal IR is constitutively active; however, this constitutive activation is impaired in diabetic retinopathy. We report a novel finding that cytoplasmic actin associates with and activates the retinal IR in vivo. We also observed that the association of actin with the IR, as well as the constitutive IR activation, is reduced under hyperglycemic conditions, in vivo. This is the first study which demonstrates that cytoplasmic actin regulates the autophosphorylation of the retinal IR. The loss of association between IR and actin may be an important contributory factor for the initial pathology of diabetic retinopathy.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 糖尿病性视网膜病是糖尿病的最常见并发症，也是工作年龄人群视力丧失的主要原因。越来越多的证据表明，在糖尿病过程中，神经视网膜在早期发生严重恶化。胰岛素受体（IR）激活已证明通过磷酸肌醇3-激酶级联反应从凋亡中挽救视网膜神经元。视网膜IR具有组成性活跃；然而，这种构型激活在糖尿病性视网膜病中受损。我们报告了一个新颖的发现，即细胞质肌动蛋白与体内的视网膜IR相关并激活视网膜IR。我们还观察到，在体外，在高血糖条件下，肌动蛋白与IR以及构型IR激活的关联降低。这是第一项研究表明，细胞质肌动蛋白调节视网膜IR的自磷酸化。 IR和肌动蛋白之间的关联丧失可能是糖尿病性视网膜病初始病理学的重要因素。