Alternative complement pathway regulation of beta cell homeostasis

β细胞稳态的替代补体途径调节

• 批准号: 10221291
• 负责人: James C Lo
• 金额: $ 37.28万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-06 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221291
• 关键词: 2019-nCoV; Accounting; Acute; Admission activity; Age; Alternative Complement Pathway; Area; Beta Cell; COVID-19; Cardiovascular Diseases; Caring; Cell Count; Cell physiology; Cells; Cessation of life; Clinical; Clinical Protocols; Clinical Treatment; Complement Activation; Country; Critical Illness; Data; Diabetes Mellitus; Disease; Epidemic; Epithelial Cells; Exhibits; Failure; Foundations; Functional disorder; Goals; Homeostasis; Hyperglycemia; Impairment; Infection; Institution; Insulin; Insulin Resistance; Intensive Care Units; Islet Cell; Islets of Langerhans; Lead; Link; Lung; Mechanical ventilation; Metabolic; Nasopharynx; New York; New York City; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Patients; Pharmaceutical Preparations; Physiological; Prevalence; Production; Prognostic Factor; Protein Array; Recording of previous events; Risk Factors; Sampling; Structure of beta Cell of islet; Testing; Translating; United States; Urban Hospitals; Viral Load result; adverse outcome; biobank; blood glucose regulation; experience; improved; indexing; metabolic phenotype; mortality; novel therapeutics; pandemic disease; prevent; protein profiling; public health relevance; 2019-nCoV; Accounting; Acute; Admission activity; Age; Alternative Complement Pathway; Area; Beta Cell; COVID-19; Cardiovascular Diseases; Caring; Cell Count; Cell physiology; Cells; Cessation of life; Clinical; Clinical Protocols; Clinical Treatment; Complement Activation; Country; Critical Illness; Data; Diabetes Mellitus; Disease; Epidemic; Epithelial Cells; Exhibits; Failure; Foundations; Functional disorder; Goals; Homeostasis; Hyperglycemia; Impairment; Infection; Institution; Insulin; Insulin Resistance; Intensive Care Units; Islet Cell; Islets of Langerhans; Lead; Link; Lung; Mechanical ventilation; Metabolic; Nasopharynx; New York; New York City; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Patients; Pharmaceutical Preparations; Physiological; Prevalence; Production; Prognostic Factor; Protein Array; Recording of previous events; Risk Factors; Sampling; Structure of beta Cell of islet; Testing; Translating; United States; Urban Hospitals; Viral Load result; adverse outcome; biobank; blood glucose regulation; experience; improved; indexing; metabolic phenotype; mortality; novel therapeutics; pandemic disease; prevent; protein profiling; public health relevance

Project Summary/Abstract Coronavirus disease of 2019 (COVID-19) is a worldwide pandemic that quickly grew from the end of 2019 to more than 5.6 million confirmed cases as of late May 2020. The number of cases is approaching 1.7 million with over 100,000 deaths in our country. Within the United States, there is tremendous regional variability in the prevalence of COVID-19 with New York State and specifically the New York City metro area being particularly hard hit. The demographic risk factors for adverse outcomes such as need for mechanical ventilation and mortality in COVID-19 include diabetes and obesity. Hyperglycemia in COVID-19 is associated with poor outcomes; however, the mechanism for hyperglycemia remains unknown. Emerging evidence show that SARS-CoV-2 could infect cells outside of the nasopharynx and lungs. ACE2 is a coreceptor for SARS-CoV-2 and is expressed on pancreatic islet cells, including beta cells. We hypothesize that SARS-CoV-2 directly infects beta cells to cause beta cell dysfunction and acute hyperglycemia. We propose to define the physiological mechanism of hyperglycemia in COVID-19 patients assessing samples from a large biobank. Understanding the mechanism for hyperglycemia may translate into clinical treatments that may improve care of COVID-19 patients.

项目摘要/摘要 2019年冠状病毒病（Covid-19）是全球大流行，迅速从 截至2020年5月下旬，2019年底到超过560万例确认案件。 在我国，案件接近170万，死亡人数超过100,000。在 美国，COVID-19的患病率有很大的区域差异 纽约州，尤其是纽约市都会区受到了特别严重的打击。 不利结果的人口统计风险因素，例如需要机械的危险因素 Covid-19的通风和死亡率包括糖尿病和肥胖。高血糖中 Covid-19与结果不佳有关；但是，高血糖的机制 仍然未知。新兴证据表明，SARS-COV-2可以感染外面的细胞 鼻咽和肺部。 ACE2是SARS-COV-2的共核能，并表示 在包括β细胞在内的胰岛细胞上。我们假设直接是SARS-COV-2 感染β细胞引起β细胞功能障碍和急性高血糖。我们建议 定义评估Covid-19患者中高血糖的生理机制 来自大型生物库的样品。了解高血糖的机制可能 转化为可以改善199例患者护理的临床治疗方法。