Novel strategies to resolve metabolic defects in the diabetic heart
解决糖尿病心脏代谢缺陷的新策略
基本信息
- 批准号:10592286
- 负责人:
- 金额:$ 47.9万
- 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:2020-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAcetylationAcetyltransferaseAddressAdvanced DevelopmentAnimal ModelAnimalsBiochemicalBioenergeticsBrainCardiacCardiac MyocytesCellsClinicalCultured CellsDataDefectDevelopmentDiabetic mouseDiseaseEnzymesExhibitsFunctional disorderFutureG-Protein-Coupled ReceptorsGlucoseGoalsHeartHeart DiseasesHeart failureHigh Fat DietImpairmentIn VitroIncidenceInsulinInterventionKnockout MiceLeft Ventricular HypertrophyLinkLiverMeasurementMediatingMetabolicMetabolic dysfunctionMetabolismMitochondriaModelingMolecularMolecular TargetMusNonesterified Fatty AcidsObesityOrphanOutputPathologicPathway interactionsPeptidesPeripheralPlayPrediabetes syndromeProductionProteinsRegulationResearchRisk FactorsRoleSignal PathwaySignal TransductionSourceStressTestingTimeTissuesWorkanalogblood glucose regulationdiabeticdiabetic cardiomyopathydiabetic patientdiabetogenicdietary controlfatty acid oxidationflexibilityfunctional declineheart functionheart metabolismimprovedin vivoknock-downmechanical energynovelnovel strategiesoxidationpeptide hormonepre-clinicalpyruvate dehydrogenasereceptorsmall moleculetooltransmission process
项目摘要
ABSTRACT
Diabetic cardiomyopathy is an independent risk factor for heart failure characterized by diastolic dysfunction
and left ventricular hypertrophy. Diabetic cardiomyopathy features striking changes in cardiomyocyte fuel
metabolism, which promote the transition into an advanced pathological state. Alterations in fuel metabolism
include an increased reliance on fatty acid oxidation for mechanical energy production, at the expense of other
substrates such as glucose. The resultant loss of metabolic flexibility can result in reduced cardiac work
efficiency and contractile dysfunction. The cellular mechanisms that drive changes in fuel substrate utilization
are not fully understood, and this deficiency represents a major impediment to the development of novel
treatments. In this proposal, we aim to investigate the utility of a novel peptide – adropin – to reverse the fuel
metabolism defects observed in diabetic cardiomyopathy. In Aim 1, we will investigate the effects of adropin on
novel cellular pathways that regulate glucose oxidation in the heart. In Aim 2, we will examine the role played
by adropin signaling pathways in regulating mitochondrial fuel metabolism. In Aim 3, we will examine whether
adropin is a candidate molecule for diabetic cardiomyopathy treatment in pre-clinical animal models. It is
expected that these studies will elucidate new cellular pathways that are central to the metabolic dysfunction
observed in diabetic cardiomyopathy, and will highlight potential new treatment pathways for this disorder.
抽象的
糖尿病心肌病是以舒张功能障碍为特征的心力衰竭的独立危险因素
和左心室肥厚。糖尿病心肌病的特点是心肌细胞燃料的显着变化
代谢,促进向高级病理状态的转变。燃料代谢的改变
包括增加对脂肪酸氧化来产生机械能的依赖,而以牺牲其他物质为代价
底物如葡萄糖。由此产生的代谢灵活性的丧失会导致心脏做功减少
效率和收缩功能障碍。驱动燃料底物利用率变化的细胞机制
尚未得到充分理解,这一缺陷是小说发展的主要障碍
治疗。在这项提案中,我们的目标是研究一种新型肽 - 阿德洛宾 - 逆转燃料的效用
糖尿病心肌病中观察到的代谢缺陷。在目标 1 中,我们将研究 adropin 对
调节心脏葡萄糖氧化的新细胞途径。在目标 2 中,我们将检查所扮演的角色
通过adropin信号通路调节线粒体燃料代谢。在目标 3 中,我们将检查是否
adropin 是临床前动物模型中治疗糖尿病心肌病的候选分子。这是
预计这些研究将阐明对代谢功能障碍至关重要的新细胞途径
在糖尿病心肌病中观察到,并将强调这种疾病的潜在新治疗途径。
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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Iain Scott其他文献
Iain Scott的其他文献
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{{ truncateString('Iain Scott', 18)}}的其他基金
Fatty acid oxidation in female cardioprotection
脂肪酸氧化对女性心脏的保护作用
- 批准号:
10534771 - 财政年份:2021
- 资助金额:
$ 47.9万 - 项目类别:
Fatty acid oxidation in female cardioprotection
脂肪酸氧化对女性心脏的保护作用
- 批准号:
10362454 - 财政年份:2021
- 资助金额:
$ 47.9万 - 项目类别:
Novel strategies to resolve metabolic defects in the diabetic heart
解决糖尿病心脏代谢缺陷的新策略
- 批准号:
10371877 - 财政年份:2020
- 资助金额:
$ 47.9万 - 项目类别:
Regulation of Fuel Utilization by Lysine Acetylation in the Failing Heart
赖氨酸乙酰化对衰竭心脏中燃料利用的调节
- 批准号:
9767853 - 财政年份:2017
- 资助金额:
$ 47.9万 - 项目类别:
Regulation of Fuel Utilization by Lysine Acetylation in the Failing Heart
赖氨酸乙酰化对衰竭心脏中燃料利用的调节
- 批准号:
9309898 - 财政年份:2017
- 资助金额:
$ 47.9万 - 项目类别:
Regulation of Fuel Utilization by Lysine Acetylation in the Failing Heart
赖氨酸乙酰化对衰竭心脏中燃料利用的调节
- 批准号:
9982397 - 财政年份:2017
- 资助金额:
$ 47.9万 - 项目类别:
Regulation of Fuel Utilization by Lysine Acetylation in the Failing Heart
赖氨酸乙酰化对衰竭心脏中燃料利用的调节
- 批准号:
9324419 - 财政年份:2016
- 资助金额:
$ 47.9万 - 项目类别:
Regulation of mitochondrial function by a novel lysine acetyltransferase
新型赖氨酸乙酰转移酶对线粒体功能的调节
- 批准号:
8424515 - 财政年份:2014
- 资助金额:
$ 47.9万 - 项目类别:
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