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

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.

项目概要/摘要 2019 年冠状病毒病 (COVID-19) 是一种全球性流行病，从 截至 2019 年底，截至 2020 年 5 月下旬确诊病例已超过 560 万例。 我国病例数接近 170 万，死亡人数超过 10 万。内 在美国，COVID-19 的流行率存在巨大的地区差异 纽约州，特别是纽约市都会区受到的打击尤其严重。 不良结果的人口统计学风险因素，例如需要机械治疗 COVID-19 中的通气和死亡率包括糖尿病和肥胖。高血糖在 COVID-19 与不良结果相关；然而，高血糖的机制 仍然未知。新证据表明 SARS-CoV-2 可以感染体外细胞 鼻咽和肺。 ACE2 是 SARS-CoV-2 的辅助受体并表达 作用于胰岛细胞，包括β细胞。我们假设 SARS-CoV-2 直接 感染β细胞导致β细胞功能障碍和急性高血糖。我们建议 定义 COVID-19 患者高血糖的生理机制评估 来自大型生物库的样本。了解高血糖的机制可能 转化为可能改善 COVID-19 患者护理的临床治疗。