Role of Pancreatic Triglycerides in Beta-cell Dysfunction

胰腺甘油三酯在β细胞功能障碍中的作用

• 批准号: 7649415
• 负责人: Ildiko Lingvay
• 金额: $ 15.12万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7649415
• 关键词: 2,4-thiazolidinedione; Adipocytes; Adipose tissue; Age; Animal Model; Apoptosis; Appearance; Award; Beta Cell; Body Weight decreased; Body mass index; Cell physiology; Choristoma; Clinical; Clinical Investigator; Country; Development; Diabetes Mellitus; Diabetes prevention; Disease; Environment; Epidemic; Ethnic Origin; Evaluation; Failure; Fatty acid glycerol esters; Functional disorder; Gender; Goals; Healthcare Systems; Heart; Human; Individual; Insulin; Insulin Resistance; Intervention; Lead; Link; Lipids; Liver; Magnetic Resonance Spectroscopy; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Modeling; Morbidity - disease rate; Muscle; Myocardium; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Operative Surgical Procedures; Organ; Pancreas; Pathogenesis; Patients; Pharmaceutical Preparations; Physicians; Pioglitazone; Prevalence; Prevention; Preventive Intervention; Procedures; Production; Public Health; Research; Research Infrastructure; Research Personnel; Resources; Risk; Rodent; Rodent Model; Role; Sampling; Science; Scientist; Structure of beta Cell of islet; Techniques; Testing; Thiazolidinediones; Time; Training; Translational Research; Triglycerides; Weight; Weight Gain; Work; bariatric surgery; career; career development; clinically significant; cost; high risk; impaired glucose tolerance; improved; innovation; intravenous glucose tolerance test; mortality; novel; patient oriented research; prevent; skills; theories; tool; volunteer

DESCRIPTION (provided by applicant): The global objective of this Mentored Patient-Oriented Research Career Development Award is to promote the candidate's career as an academic physician-scientist and to facilitate her transition to an independent investigator. To accomplish this goal, the candidate and her mentors have developed an integrated plan that combines an innovative idea of great clinical significance, cutting-edge science and advanced training in the techniques of patient-oriented research. LIT Southwestern provides a great infrastructure and an excellent academic environment to support the career development of young clinical investigators. This award will provide the candidate with the time, resources, and skills necessary for clinical and translational research in the field of diabetes. The proposed research plan will test if the lipotoxicity mechanism is a significant contributor to beta-cell dysfunction in humans. It is hypothesized that pancreatic triglyceride (fat) accumulation contributes to betacell failure and the development of type 2 diabetes. The relationship between ectopic fat acumulation in the pancreas and beta-cell function will be determined in Aim 1. In Aim 2 subjects planning to undergo bariatric surgery will be evaluated and followed for 1 year after the procedure. Changes in pancreatic fat content, beta-cell function, and insulin resistance will be described. The third Aim will assess if a drug intervention (pioglitazone) will reduce fat accumulation in the pancreas alongside with improvement of beta-cell function. A novel non-invasive magnetic resonance spectroscopy technique will be used to accurately and reliably quantify pancreatic fat content. Improved understanding of the pathophysiology of type 2 diabetes will aid the development of effective agents for diabetes prevention and even cure. Since type 2 diabetes has become so prevalent and is associated with high morbidity and mortality, such work has significant public health impact. Also, if pancreatic fat quantification proves to be a good predictor of beta-cell function, this novel non-invasive test could develop into a valuable clinical tool used to accurately predict the development of diabetes in high-risk subjects. The combination of advanced training in patient-oriented research and in-depth study of an important clinical problem will prepare the candidate for a Iong-term career as an independent investigator.

描述（由申请人提供）：这项受过指导的患者研究职业发展奖的全球目标是促进候选人作为学术医师科学家的职业，并促进她向独立研究者的过渡。为了实现这一目标，候选人和她的导师制定了一项综合计划，该计划结合了一个具有巨大临床意义，尖端科学和高级培训的创新思想，以患者为导向的研究。 LIT Southwestern提供了一个很好的基础设施和一个绝佳的学术环境，以支持年轻临床研究人员的职业发展。该奖项将为候选人提供糖尿病领域临床和转化研究所需的时间，资源和技能。 拟议的研究计划将测试脂肪毒性机制是否是导致人类β细胞功能障碍的重要原因。假设胰腺甘油三酸酯（脂肪）的积累有助于Betacell衰竭和2型糖尿病的发展。在AIM 1中，将确定胰腺中异位脂肪效果与Beta细胞功能之间的关系。在AIM 2中，计划进行减肥手术的受试者将进行评估，并在手术后1年遵循。将描述胰腺脂肪含量，β细胞功能和胰岛素抵抗的变化。第三个目标将评估药物干预（吡格列酮）是否会随着β细胞功能的改善而减少胰腺中的脂肪积累。一种新型的非侵入性磁共振光谱技术将用于准确，可靠地量化胰腺脂肪含量。 对2型糖尿病的病理生理学的理解有助于开发预防糖尿病甚至治愈的有效药物。由于2型糖尿病已经变得如此普遍，并且与高发病率和死亡率有关，因此这种工作具有重大的公共卫生影响。同样，如果胰腺脂肪定量被证明是β细胞功能的良好预测指标，那么这种新型的非侵入性测试可能会发展为一种有价值的临床工具，用于准确预测高风险受试者中糖尿病的发展。对重要临床问题的高级研究和深入研究的高级培训的结合将使候选人成为IONG期间职业生涯的独立研究者。