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.

抽象的随着人口迅速增长的迅速增长，与年龄相关的疾病已成为对健康的日益威胁。一个例子是2型糖尿病（T2D），一种以高血糖水平为特征的慢性疾病由于胰岛素分泌和胰岛素抵抗受损。大约9％的美国人口患有糖尿病，随着年龄的增长而增加的流行率； 65岁或以上的美国人的事件率三倍。衰老是缺乏细胞分裂和组织更新的过程，是导致衰老和年龄的重要因素相关疾病。越来越多的证据已经建立了细胞感应和糖尿病之间的联系。胰腺β细胞感应已被暗示是T2D的促进者，这表明通过随着β细胞功能和质量的下降是T2D的标志，哪种感应有助于糖尿病进展。但是，T2D进展过程中感应的发育和动力学尚不清楚，并且评估可用的感应靶向疗法仅限于组织水平，主要是由于缺乏识别胰岛中的感觉细胞的敏感工具，尤其是体内。在这项研究中，我们提出开发分子探针，以实时检测胰岛中的感应，我们将评估分离的胰岛和体内T2D小鼠模型中的探针。该项目的完成将生成一种新型的分子探针，用于实时检测胰岛中的感应。这将是必不可少的工具，用于研究糖尿病中的感应和验证的合理性衰老是预防和治疗T2D的治疗靶标。相同的探针设计策略也可以用于为其他与年龄有关的疾病开发问题。