Specific senescence detection in pancreatic islets

胰岛的特异性衰老检测

基本信息

批准号：
10648322
负责人：
Lina Cui
金额：
$ 41.94万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2025-09-14
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10648322
关键词：
Affinity Age Aging American Animal Model Animals B-Lymphocytes Beta Cell Binding Biological Markers Blood Glucose Cardiovascular Diseases Cell Aging Cell Cycle Arrest Cell division Cell physiology Cells Chronic Clinical Cytoplasmic Granules Data Detection Development Diabetes Mellitus Diabetic mouse Diet Disease Disease model Drug usage Endocrine Evaluation Excision Feedback Fibrosis Functional disorder Generations Glyburide Goals Health Healthcare Systems High Fat Diet Homeostasis Image Impairment Incidence Inflammation Insulin Insulin Resistance Intervention Islet Cell Islets of Langerhans Kinetics Knockout Mice Lead Link Molecular Probes Mus Neurodegenerative Disorders Non-Insulin-Dependent Diabetes Mellitus Organ Organism Pancreas Population Prevalence Prevention Process Proliferating Proteins Public Health Role Secretory Vesicles Series Signal Transduction Specificity Structure of beta Cell of islet Therapeutic Time Tissues Tumor Suppression Tumor Tissue Validation age group age related aged aging population animal imaging cell injury chromogranin B design diabetes pathogenesis exhaustion in vivo in vivo Model in vivo imaging inhibitor insulin secretion islet knockout gene mouse model novel overexpression prevent real time monitoring real-time images senescence serial imaging stem cells sulfonylurea receptor targeted treatment therapeutic target tissue regeneration tool

项目摘要

Abstract With the rapidly growing aging population, age-related diseases have become an increasing threat to health. One such example is type 2 diabetes (T2D), a chronic condition characterized by high blood glucose levels due to impaired insulin secretion and insulin resistance. Around 9% of the American population has diabetes, the prevalence of which increases with age; the incidence rate triples in Americans aged 65 or older. Senescence, a process lacking cell division and tissue renewal, is an essential contributor to aging and age- related diseases. Mounting evidence has established links between cellular senescence and diabetes. Pancreatic β cell senescence has been implicated as a contributor to T2D, suggesting a mechanism through which senescence contributes to diabetes, as the decline of β cell function and mass is a hallmark of T2D progression. However, the development and kinetics of senescence during the progression of T2D is unknown, and the evaluation of available senescence-targeting therapies is limited to the tissue level, primarily due to the lack of sensitive tools for identifying senescent cells in pancreatic islets, particularly in vivo. In this study, we propose to develop a molecular probe for the real-time detection of senescence in pancreatic islets, and we will evaluate the probe in isolated pancreatic islets and in T2D mice models in vivo. Completion of the project will generate a novel molecular probe for the real-time detection of senescence in pancreatic islets. It will be an indispensable tool for the study of senescence in diabetes, and for the validation of the plausibility of senescence as a therapeutic target for the prevention and treatment of T2D. The same probe design strategy can also be used to develop probes for other age-related diseases.

抽象的随着人口老龄化的迅速增长，与年龄相关的疾病已成为日益严重的健康威胁。 2 型糖尿病 (T2D) 就是一个这样的例子，这是一种以高血糖水平为特征的慢性疾病由于胰岛素分泌受损和胰岛素抵抗，大约 9% 的美国人患有糖尿病，其患病率随着年龄的增长而增加；65 岁或以上的美国人的发病率增加了三倍。衰老是一个缺乏细胞分裂和组织更新的过程，是衰老和年龄增长的重要因素。越来越多的证据表明细胞衰老与糖尿病之间存在联系。胰腺 β 细胞衰老被认为是 T2D 的一个促成因素，这表明了一种机制：衰老会导致糖尿病，因为 β 细胞功能和质量的下降是 T2D 的标志然而，T2D 进展过程中衰老的发展和动力学尚不清楚，现有的衰老靶向疗法的评估仅限于组织水平，这主要是由于缺乏敏感的工具来识别胰岛中的衰老细胞，特别是在本研究中。提出开发一种实时检测胰岛衰老的分子探针，我们将该项目将在离体胰岛和 T2D 小鼠模型中进行体内评估。产生一种用于实时检测胰岛衰老的新型分子探针。研究糖尿病衰老以及验证其合理性的不可或缺的工具衰老作为预防和治疗 T2D 的治疗靶点相同的探针设计策略。也可用于开发其他与年龄相关的疾病的探针。