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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.

摘要随着人口老龄化的快速增长，与年龄相关的疾病已成为对健康的威胁。一个这样的例子是2型糖尿病（T2 D），一种以高血糖水平为特征的慢性病症这是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，其患病率随年龄增长而增加;在65岁或以上的美国人中发病率是原来的三倍。衰老是一个缺乏细胞分裂和组织更新的过程，是衰老和衰老的重要因素。相关疾病。越来越多的证据已经确定了细胞衰老和糖尿病之间的联系。胰腺β细胞衰老被认为是T2 D的一个促成因素，这表明了一种机制，衰老导致糖尿病，因为β细胞功能和质量的下降是T2 D的标志进展然而，T2 D进展期间衰老的发展和动力学是未知的，并且对可用的衰老靶向疗法的评估仅限于组织水平，主要是由于缺乏用于鉴定胰岛中衰老细胞的敏感工具，特别是在体内。本研究建议开发一种实时检测胰岛衰老的分子探针，我们将在分离的胰岛和体内T2 D小鼠模型中评价探针。建成后将产生用于实时检测胰岛衰老的新型分子探针。这将是一这是研究糖尿病衰老和验证衰老作为预防和治疗T2 D的治疗靶点。相同的探头设计策略也可用于开发其他年龄相关疾病的探针。