权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The Role of Oxidative Phosphorylation Complexes in Beta Cell Biology

氧化磷酸化复合物在 β 细胞生物学中的作用

基本信息

批准号：
10369626
负责人：
Anna L Lang
金额：
$ 6.98万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369626
关键词：
Affect Animals Antioxidants Area Beta Cell Biological Markers Biosensor Calcium Cardiomyopathies Cell Death Cell Energetics Cell membrane Cell physiology Cellular biology Chronic Collaborations Complex Coupling Critical Thinking Cytosol Data Defect Development Diabetes Mellitus Disease Electron Transport Complex III Environment Exocytosis Experimental Designs Functional disorder Glucose Goals Human Hyperglycemia Individual Inflammation Inherited Inner mitochondrial membrane Insulin Knock-out Knowledge Laboratories Lead Learning Mediating Mentors Metabolic Metabolism Mitochondria Mitochondrial Diseases Modeling Morphology Mus Nerve Degeneration Neurons Oxidative Phosphorylation Oxidative Stress Pancreas Pathogenicity Pathologic Pathology Pathway interactions Patients Phenotype Physiology Process Production Reactive Oxygen Species Research Respiration Role Sampling Signal Pathway Stimulus Structure of beta Cell of islet System Technical Expertise Testing Training Translating Work base blood glucose regulation cell type complex IV diabetes pathogenesis diabetic endoplasmic reticulum stress glucose production human disease in vivo insight insulin granule insulin secretion insulin signaling islet mitochondrial dysfunction mitochondrial metabolism mouse model novel protein complex protein expression response

项目摘要

Project Summary The insulin-secreting pancreatic beta cell is a highly metabolic cell type and its dysfunction is a main cause of diabetes pathogenesis. The beta cell is reliant on mitochondrial function and energy production for glucose- stimulated insulin secretion. Mitochondrial ATP production is accomplished by 5 multi-subunit complexes of the oxidative phosphorylation (OXPHOS) system. The increase in the ATP:ADP ratio in the beta cell cytosol is the triggering signal for insulin release. Although a net decrease in ATP production would have an impact on beta cell function and insulin secretion, the impact of individual OXPHOS complex defects on beta cell biology and function remains unknown. Indeed, there are a broad spectrum of human diseases caused by defects in individual OXPHOS complexes ranging from neurodegeneration to cardiomyopathies, including maternally- inherited diabetes, suggesting a diverse range of downstream pathomechanisms. Therefore, the objective of this proposal is to elucidate the impact of three individual OXPHOS complexes (Complex I, III, and IV) in the context of the pancreatic beta cell. The hypothesis is that defects in individual OXPHOS complexes will result in distinct signaling pathway changes that will alter beta cell biology. Based on preliminary data, it is also hypothesized that Complex III deficient islets develop a severe hyperglycemic phenotype due to increased production of reactive oxygen species and oxidative stress. This proposal and training plan will provide the applicant with an excellent training environment with two recognized experts in islet physiology and mitochondrial diseases as co-mentors. Being a collaboration between two laboratories will allow the applicant ample opportunities to broaden her knowledge of a new research area, learn new scientific models and technical skills, enhance her critical thinking and rigorous experimental design, and set the stage to translate research questions to human pancreatic samples.

Please try later.