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Effects of Exercise and GLP-1R Agonism on Muscle Microvascular Perfusion and Insulin Action

运动和 GLP-1R 激动对肌肉微血管灌注和胰岛素作用的影响

基本信息

批准号：
10614454
负责人：
ZHENQI LIU
金额：
$ 65.68万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10614454
关键词：
Acute Address Adult Affect Agonist Applications Grants Area Attenuated Biopsy Blood Vessels Blood Volume Blood capillaries Body Weight Cardiac Cardiovascular system Closure by clamp Coronary Data Death Rate Diabetes Mellitus Diabetes prevention Diagnostic Endothelium Equilibrium Event Exercise Exhibits Future GLP-I receptor High Fat Diet Human Impairment Insulin Insulin Resistance Intervention Life Style Modification Light Mediating Metabolic Metabolic syndrome Microcirculation Mitochondria Morbidity - disease rate Mus Muscle Muscle Cells Myocardial Infarction Myocardium Non-Insulin-Dependent Diabetes Mellitus Obesity Pathogenesis Patients Perfusion Physical activity Prediabetes syndrome Prevention Receptor Activation Regulation Relaxation Reporting Resistance Rodent Model Role Skeletal Muscle Stroke Surface Techniques Testing Therapeutic Studies angiogenesis arteriole cardiorespiratory fitness cardiovascular disorder prevention cardiovascular effects cardiovascular risk factor contrast enhanced density exercise training glucagon-like peptide 1 improved liraglutide mortality patient population preservation prevent recruit response skeletal translational approach ultrasound

项目摘要

Project Summary/Abstract Patients with metabolic syndrome exhibit metabolic insulin resistance, have increased risks of cardiovascular events and are prone to developing type 2 diabetes mellitus. Substantial evidence has established the value of high levels of physical activity, exercise training, and overall cardiorespiratory fitness in the prevention of cardiovascular diseases. Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to reduce the new onset of diabetes in adult humans with prediabetes and the rate of major adverse cardiovascular events among patients with type 2 diabetes. The mechanisms underpinning the cardiovascular benefits of exercise and GLP-1 receptor agonism remain elusive. In the proposed studies, we will test an overarching hypothesis that exercise and GLP-1 receptor agonism each enhance insulin-mediated microvascular perfusion and muscle angiogenesis, leading to increased muscle delivery and action of insulin in the insulin resistant state. We further hypothesize that the combination of both would be more effective. We will use a translational approach to examine the effects of exercise and GLP-1 receptor agonism on both skeletal muscle and coronary microvasculature in humans with metabolic syndrome and the role of endothelial AMPK and mitochondrial fission in the pathogenesis of microvascular insulin resistance. We will use a state-of-the-art technique, contrast-enhanced ultrasound, in combination with arteriovenous balance, muscle biopsy and insulin clamp to quantify the effects of exercise training and GLP-1 receptor agonism on microvascular and metabolic responses to insulin in humans with insulin resistance/metabolic syndrome and open a new avenue for future mechanistic and/or therapeutic studies. We will further use a variety of rodent models to explore the underlying mechanisms. By understanding the regulation of skeletal and cardiac muscle microvascular function and insulin responses in humans with metabolic syndrome, it may be possible to correct vascular and ameliorate metabolic insulin resistance to prevent diabetes and decrease the associated cardiovascular risks.

项目总结/文摘