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:10027190
- 负责人:
- 金额:$ 65.68万
- 依托单位:
- 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 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAdultAffectAgonistApplications GrantsAreaAttenuatedBiopsyBlood VesselsBlood VolumeBlood capillariesBody WeightCardiacCardiovascular systemClosure by clampCoronaryDataDeath RateDiabetes MellitusDiabetes preventionDiagnosticEndotheliumEquilibriumEventExerciseExhibitsFutureGLP-I receptorHigh Fat DietHumanImpairmentInsulinInsulin ResistanceInterventionLife Style ModificationLightMediatingMetabolicMetabolic syndromeMicrocirculationMitochondriaMorbidity - disease rateMusMuscleMuscle CellsMyocardial InfarctionMyocardiumNon-Insulin-Dependent Diabetes MellitusObesityPathogenesisPatientsPerfusionPhysical activityPrediabetes syndromePreventionReceptor ActivationRegulationReportingResistanceRodent ModelRoleSkeletal MuscleStrokeSurfaceTechniquesTestingTherapeutic StudiesUltrasonographyangiogenesisarteriolecardiorespiratory fitnesscardiovascular disorder preventioncardiovascular risk factorcontrast enhanceddensityexercise trainingglucagon-like peptide 1improvedinsulin sensitizing drugsliraglutidemortalitypatient populationpreservationpreventrecruitresponseskeletaltranslational approach
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/摘要
代谢综合征患者表现出代谢性胰岛素抵抗,增加
心血管事件的风险,并容易发展为2型糖尿病。
大量的证据已经证明了高水平的身体活动的价值,
运动训练和整体心肺健康,
心血管疾病胰高血糖素样肽1(GLP-1)受体激动剂已被广泛应用于临床。
显示出减少患有前驱糖尿病的成年人的糖尿病新发,
2型糖尿病患者主要心血管不良事件发生率。的
运动和GLP-1受体的心血管益处的基础机制
激动作用仍然难以捉摸。在拟议的研究中,我们将测试一个总体假设,
运动和GLP-1受体激动各自增强胰岛素介导的
微血管灌注和肌肉血管生成,导致肌肉输送增加
以及胰岛素抵抗状态下胰岛素的作用。我们进一步假设,
两者的结合会更有效。我们将使用翻译方法,
检查运动和GLP-1受体激动剂对骨骼肌
和冠状动脉微血管系统的作用
内皮细胞AMPK和线粒体分裂在微血管胰岛素发病机制中的作用
阻力我们将使用最先进的技术超声造影
结合动静脉平衡、肌肉活检和胰岛素钳夹定量
运动训练和GLP-1受体激动剂对微血管和
胰岛素抵抗/代谢综合征患者对胰岛素的代谢反应
并为未来的机制和/或治疗研究开辟了新的途径。我们将
进一步使用各种啮齿动物模型来探索潜在的机制。通过
了解骨骼肌和心肌微血管功能的调节,
在代谢综合征患者的胰岛素反应中,
改善代谢性胰岛素抵抗,预防糖尿病,
相关的心血管风险。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('ZHENQI LIU', 18)}}的其他基金
Role of Microvascular insulin resistance and cardiorespiratory fitness in diabetes
微血管胰岛素抵抗和心肺健康在糖尿病中的作用
- 批准号:
10371154 - 财政年份:2021
- 资助金额:
$ 65.68万 - 项目类别:
Role of Microvascular insulin resistance and cardiorespiratory fitness in diabetes
微血管胰岛素抵抗和心肺健康在糖尿病中的作用
- 批准号:
10212038 - 财政年份:2021
- 资助金额:
$ 65.68万 - 项目类别:
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
- 批准号:
10170355 - 财政年份:2020
- 资助金额:
$ 65.68万 - 项目类别:
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
- 批准号:
10614454 - 财政年份:2020
- 资助金额:
$ 65.68万 - 项目类别:
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
- 批准号:
10396551 - 财政年份:2020
- 资助金额:
$ 65.68万 - 项目类别:
Insulin action in human cardiac and skeletal muscle microvasculature
胰岛素在人体心脏和骨骼肌微血管中的作用
- 批准号:
8223319 - 财政年份:2010
- 资助金额:
$ 65.68万 - 项目类别:
CANDESARTAN EFFECT ON CARDIAC & SKELETAL MUSCLE RESPONSE TO INSULIN
坎地沙坦对心脏的影响
- 批准号:
8167204 - 财政年份:2010
- 资助金额:
$ 65.68万 - 项目类别:
Insulin action in human cardiac and skeletal muscle microvasculature
胰岛素在人体心脏和骨骼肌微血管中的作用
- 批准号:
8625818 - 财政年份:2010
- 资助金额:
$ 65.68万 - 项目类别:
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