Diet-Induced Insulin Resistance and Myocardial Ischemia in Pigs
饮食引起的猪胰岛素抵抗和心肌缺血
基本信息
- 批准号:7618190
- 负责人:
- 金额:$ 41.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1994
- 资助国家:美国
- 起止时间:1994-02-01 至 2009-05-31
- 项目状态:已结题
- 来源:
- 关键词:1-Phosphatidylinositol 3-Kinase2,4-thiazolidinedioneAcute myocardial infarctionAddressAffectAgonistAngina PectorisAnimal ModelAnimalsAtherosclerosisAttenuatedCarbohydratesCardiacCardiolipinsCardiovascular systemCell RespirationChestChronicClinicalComplexConditionCountryDataDevelopmentDiabetes MellitusDietExhibitsFamily suidaeFat-Restricted DietFibratesFunctional disorderGene ExpressionGene ProteinsGenetic ModelsGoalsHeartHumanInfarctionInsulinInsulin ResistanceIschemiaKnowledgeLinkLipidsMeasurementMetabolicMetabolismModelingMorbidity - disease rateMyocardialMyocardial IschemiaMyocardial dysfunctionMyocardiumNon-Insulin-Dependent Diabetes MellitusNonesterified Fatty AcidsObesityOutcomePPAR alphaPathologicPathway interactionsPatientsPeroxisome Proliferator-Activated ReceptorsPharmaceutical PreparationsPhysiological reperfusionPopulationRecoveryRecovery of FunctionReperfusion InjuryReperfusion TherapyRodentRodent ModelSignal TransductionSus scrofaTestingThiazolidinedionesUnited StatesUnstable anginaacute coronary syndromecardiovascular risk factorfatty acid metabolismfeedinginsulin signalinglipid metabolismmortalitymyocardial infarct sizingoutcome forecastprotein expressionpyruvate dehydrogenaseresearch studyresponsesaturated fatsizesugartool
项目摘要
PROJECT SUMMARY:
Two thirds of patients with acute myocardial infarction or unstable angina pectoris have
underlying insulin resistance. Insulin resistance is an independent factor portending poor
short and long-term prognosis in these patients. Hearts of insulin-resistant rodents
exhibit abnormal carbohydrate and lipid metabolism that may be causally related to
impaired functional recovery after ischemia and reperfusion (I/R). However, rodent
models are limited by dissimilarities to human cardiac function, metabolism, and gene
and protein expression. A large animal model of insulin resistance would be an important
tool in bridging rodent and human pathophysiology in this condition. This study will test
the hypothesis that diet-induced insulin resistance in pigs causes pathologic alterations
of myocardial carbohydrate and lipid metabolism that adversely affect the response to
I/R. Pigs fed a diet high in saturated fat and simple sugars develop obesity and insulin
resistance over several months; they are compared to lean controls fed a low-fat diet
with no added sugar. Under anesthetized, open-chest conditions, pigs undergo low-flow
myocardial I/R with concomitant measurements of cardiac contractile function, substrate
utilization, and gene expression. Experiments will determine whether diminished
recovery of contractile function in insulin-resistant pigs is related to myocardial insulin
resistance due to impaired signaling through the phosphatidylinositol-3-kinase pathway,
decreased activity of pyruvate dehydrogenase, altered myocardial free fatty acid
metabolism and/or lipid accumulation, or alterations of cardiolipin content and
composition. Peroxisome proliferator-activated receptors (PPARs) are critical regulators
of substrate metabolism whose expression and function in myocardium may be altered
by insulin resistance. Moreover, many patients with insulin resistance are treated with
PPAR agonist drugs (fibrates, thiazolidinediones) despite little knowledge of their cardiac
effects. Therefore, an additional goal is to determine whether chronic treatment with a
PPAR alpha or gamma agonist modifies myocardial metabolic and contractile
dysfunction after I/R in insulin resistant pigs.
项目总结:
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(1)
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GREGORY G SCHWARTZ其他文献
GREGORY G SCHWARTZ的其他文献
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{{ truncateString('GREGORY G SCHWARTZ', 18)}}的其他基金
Diet-Induced Insulin Resistance and Myocardial Ischemia in Pigs
饮食引起的猪胰岛素抵抗和心肌缺血
- 批准号:
8069630 - 财政年份:1994
- 资助金额:
$ 41.96万 - 项目类别:
Diet-Induced Insulin Resistance and Myocardial Ischemia in Pigs
饮食引起的猪胰岛素抵抗和心肌缺血
- 批准号:
7845092 - 财政年份:1994
- 资助金额:
$ 41.96万 - 项目类别:
Protection by Thiazolidinediones in Myocardial Ischemia
噻唑烷二酮类药物对心肌缺血的保护作用
- 批准号:
6604250 - 财政年份:1994
- 资助金额:
$ 41.96万 - 项目类别:
Protection by Thiazolidinediones in Myocardial Ischemia
噻唑烷二酮类药物对心肌缺血的保护作用
- 批准号:
6436621 - 财政年份:1994
- 资助金额:
$ 41.96万 - 项目类别:
Diet-Induced Insulin Resistance and Myocardial Ischemia in Pigs
饮食引起的猪胰岛素抵抗和心肌缺血
- 批准号:
8280242 - 财政年份:1994
- 资助金额:
$ 41.96万 - 项目类别:
Protection by Thiazolidinediones in Myocardial Ischemia
噻唑烷二酮类药物对心肌缺血的保护作用
- 批准号:
7087019 - 财政年份:1994
- 资助金额:
$ 41.96万 - 项目类别: