Metabolic Effects of Augmenting Pulsatile Growth Hormone Secretion in HIV-Infecti
增加 HIV 感染者脉动生长激素分泌的代谢效应
基本信息
- 批准号:8010298
- 负责人:
- 金额:$ 15.89万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-19 至 2015-06-30
- 项目状态:已结题
- 来源:
- 关键词:AbdomenAdipose tissueAdultAdverse effectsAffectAftercareApplications GrantsAtrophicAttentionAwardBody CompositionBody fatCardiacCardiovascular DiseasesCentral obesityChildhoodClinicalClinical InvestigatorClinical ResearchClinical TrialsComorbidityCross-Over StudiesDataDevelopmentDevelopment PlansDiabetes MellitusDoseDouble-Blind MethodDyslipidemiasEndocrineEndocrinologistFaceFatty acid glycerol estersFeedbackFundingGlucoseGoalsHIVHIV InfectionsHepaticHighly Active Antiretroviral TherapyHormonesHumanIndividualInfusion proceduresInsulinInsulin ResistanceInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor IInsulin-Like Growth-Factor-Binding ProteinsInvestigationKnowledgeLeadLimb structureLipidsLipodystrophyLipolysisLiverLong-Term EffectsMagnetic Resonance SpectroscopyMeasurementMeasuresMentorsMentorshipMetabolicMetabolismMethodologyMethodsModelingMuscleOGTTObesityParentsPatientsPatternPeripheralPhysiologic pulsePhysiologicalPhysiologyPlacebosPopulationProductionProtocols documentationRecombinantsResearchResearch InfrastructureResearch PersonnelRiskRisk FactorsSliceSomatotropinSomatotropin-Releasing HormoneTechniquesTherapeuticTimeTracerTrainingUnited States National Institutes of HealthVisceralWithdrawalX-Ray Computed Tomographyabdominal fatantiretroviral therapyblood glucose regulationcardiovascular disorder riskcareercareer developmentcoronary artery calcificationdepot-insulindesigndrug developmentexperienceglucose metabolismglucose uptakegrowth hormone deficiencyimprovedinsulin sensitivitylipid metabolismmortalitynovel strategiespatient oriented researchpublic health relevancer-hGH-Mrandomized placebo controlled trialresponseskillsskills trainingstable isotopestatisticsstemsuccesssugartherapy developmenttreatment strategy
项目摘要
DESCRIPTION (provided by applicant): More than half of individuals treated for HIV-infection now demonstrate changes in body fat distribution, including increased visceral adiposity and peripheral fat atrophy. Along with these changes, HIV-infected patients are at increased risk for insulin resistance, diabetes, dyslipidemia, and cardiovascular disease. This grant proposal investigates a novel strategy to decrease abdominal fat and reduce metabolic risk in HIV- infection by augmenting endogenous growth hormone (GH) secretion through the use of growth hormone releasing hormone (GHRH1-44). The rationale for this strategy stems from data that HIV-infected patients with abdominal fat accumulation are relatively GH deficient, and from clinical observations that GH replacement in other populations with GH deficiency improves body composition and ameliorates cardiometabolic risk. The use of GHRH1-44 in this application, in contrast to the use of exogenous recombinant human GH (rhGH), is proposed in order to augment physiologic pituitary GH secretion rather than providing apulsatile exogenous replacement. Our preliminary data demonstrate that GHRH1-44 increases endogenous pulsatile growth hormone secretion, which we hypothesize will lead to greater efficacy and reduced side effects as compared to exogenous rhGH. Previous studies have demonstrated that GHRH1-44 reduces visceral fat accumulation and improves dyslipidemia. In this proposal we hypothesize that GHRH1-44 will also decrease ectopic fat in liver and muscle, potentially ameliorating insulin resistance. Two studies are proposed in this application - a short-term comparison of the effects of GHRH1-44 vs. rhGH on endogenous GH pulsatility and insulin sensitivity, and a 1 year randomized placebo-controlled trial measuring the effects of GHRH1-44 on lipolysis, insulin sensitivity, and ectopic fat accumulation. Together, data from these studies will characterize the metabolic effects GHRH1- 44 and, additionally, will explore the physiologic importance of GH pulsatility by contrasting the effects of GHRH1-44 vs. rhGH. With these goals, the proposed research will both enhance our understanding of GH physiology and contribute to the development of a potentially important new treatment strategy for metabolic complications of HIV.
The candidate in this application, Dr. Takara Stanley, is a pediatric endocrinologist with clinical research experience in metabolic and endocrine complications of HIV-infection. Dr. Stanley's career goal is to perform patient-oriented research in an academic setting, focusing on the metabolic and endocrine aspects of body fat distribution. In the current proposal, Dr. Stanley will explore these themes through the model of HIV-lipodystrophy. As she progresses in her career, she plans to expand her field of investigation to pediatric conditions of abdominal obesity. The proposed studies will provide Dr. Stanley with experience and training in numerous methods of physiologic investigation, including techniques for analyzing hormone secretory dynamics, glucose homeostasis, and lipid metabolism. In addition, the proposed career development plan will provide Dr. Stanley will further training in statistics and drug development. The mentor in this proposal, Dr. Steven Grinspoon, is an internationally recognized expert in the field of HIV-associated endocrine and metabolic complications. In addition to being a well-established and well-funded clinical researcher, he is an accomplished mentor with the skills and infrastructure necessary to mentor Dr. Stanley and help her transition to independence. Along with the mentorship of Dr. Grinspoon, the career development plan proposed in this application will provide Dr. Stanley with the training and skills to become an independent clinical investigator.
PUBLIC HEALTH RELEVANCE: This project will determine the metabolic effects of a new therapy, growth hormone releasing hormone (GHRH1-44), to reduce abdominal fat and improve metabolism in patients with HIV-infection and increased belly size. The research will contribute to our knowledge of this important potential therapy for complications of HIV-infection, and will also increase our understanding of how growth hormone affects sugar and fat metabolism.
描述(由申请人提供):超过一半的HIV感染治疗的个体现在表现出体脂分布的变化,包括内脏肥胖增加和外周脂肪萎缩。沿着这些变化,HIV感染者患胰岛素抵抗、糖尿病、血脂异常和心血管疾病的风险增加。这项拨款提案调查了一种新的策略,通过使用生长激素释放激素(GHRH 1 -44)增加内源性生长激素(GH)分泌,减少腹部脂肪和降低HIV感染的代谢风险。这一策略的基本原理源于数据,即腹部脂肪堆积的HIV感染患者相对缺乏GH,并从临床观察,GH缺乏的其他人群中的GH替代改善身体成分和改善心脏代谢风险。与使用外源性重组人GH(rhGH)相比,本申请中使用GHRH 1 -44是为了增加生理垂体GH分泌,而不是提供替代性外源性替代。我们的初步数据表明,GHRH 1 -44增加内源性脉动生长激素分泌,我们假设这将导致更大的疗效和减少的副作用相比,外源性rhGH。先前的研究表明,GHRH 1 -44可以减少内脏脂肪堆积,改善血脂异常。在这个提议中,我们假设GHRH 1 -44也会减少肝脏和肌肉中的异位脂肪,可能改善胰岛素抵抗。本申请中提出了两项研究-GHRH 1 -44与rhGH对内源性GH脉动性和胰岛素敏感性影响的短期比较,以及一项测量GHRH 1 -44对脂解、胰岛素敏感性和异位脂肪蓄积影响的1年随机安慰剂对照试验。总之,这些研究的数据将表征GHRH 1 - 44的代谢效应,此外,还将通过对比GHRH 1 -44与rhGH的效应来探索GH脉动性的生理重要性。有了这些目标,拟议的研究将提高我们对GH生理学的理解,并有助于开发一种潜在的重要的新的HIV代谢并发症治疗策略。
本申请的候选人Takara Stanley博士是一名儿科内分泌学家,在HIV感染的代谢和内分泌并发症方面具有临床研究经验。斯坦利博士的职业目标是在学术环境中进行以患者为导向的研究,重点是身体脂肪分布的代谢和内分泌方面。在目前的提案中,Stanley博士将通过HIV脂肪营养不良模型探索这些主题。随着她事业的发展,她计划将她的研究领域扩大到腹部肥胖的儿科疾病。拟议的研究将为Stanley博士提供多种生理学研究方法的经验和培训,包括分析激素分泌动力学、葡萄糖稳态和脂质代谢的技术。此外,拟议的职业发展计划将为Stanley博士提供统计和药物开发方面的进一步培训。该提案的导师Steven Grinspoon博士是艾滋病毒相关内分泌和代谢并发症领域的国际公认专家。除了是一个成熟和资金充足的临床研究人员,他是一个有成就的导师与必要的技能和基础设施,以指导斯坦利博士,并帮助她过渡到独立。沿着Grinspoon博士的指导,本申请中提出的职业发展计划将为Stanley博士提供培训和技能,使其成为一名独立的临床研究者。
公共卫生关系:该项目将确定一种新疗法,生长激素释放激素(GHRH 1 -44)的代谢作用,以减少腹部脂肪,改善HIV感染和腹部增大患者的代谢。这项研究将有助于我们了解这种重要的潜在治疗艾滋病毒感染并发症的方法,也将增加我们对生长激素如何影响糖和脂肪代谢的理解。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Takara Leah Stanley其他文献
Takara Leah Stanley的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Takara Leah Stanley', 18)}}的其他基金
Augmenting Pulsatile Growth Hormone: Metabolic Effects in HIV-Infection
增强脉动生长激素:HIV 感染中的代谢效应
- 批准号:
8488437 - 财政年份:2010
- 资助金额:
$ 15.89万 - 项目类别:
Augmenting Pulsatile Growth Hormone: Metabolic Effects in HIV-Infection
增强脉动生长激素:HIV 感染中的代谢效应
- 批准号:
8307415 - 财政年份:2010
- 资助金额:
$ 15.89万 - 项目类别:
Augmenting Pulsatile Growth Hormone: Metabolic Effects in HIV-Infection
增强脉动生长激素:HIV 感染中的代谢效应
- 批准号:
8113351 - 财政年份:2010
- 资助金额:
$ 15.89万 - 项目类别:
Growth Hormone Releasing Hormone in Patients with HIV Lipodystrophy
HIV 脂肪营养不良患者的生长激素释放激素
- 批准号:
7642388 - 财政年份:2008
- 资助金额:
$ 15.89万 - 项目类别:
Growth Hormone Releasing Hormone in Patients with HIV Lipodystrophy
HIV 脂肪营养不良患者的生长激素释放激素
- 批准号:
7417292 - 财政年份:2008
- 资助金额:
$ 15.89万 - 项目类别:
相似海外基金
Deciphering the role of adipose tissue in common metabolic disease via adipose tissue proteomics
通过脂肪组织蛋白质组学解读脂肪组织在常见代谢疾病中的作用
- 批准号:
MR/Y013891/1 - 财政年份:2024
- 资助金额:
$ 15.89万 - 项目类别:
Research Grant
ESTABLISHING THE ROLE OF ADIPOSE TISSUE INFLAMMATION IN THE REGULATION OF MUSCLE MASS IN OLDER PEOPLE
确定脂肪组织炎症在老年人肌肉质量调节中的作用
- 批准号:
BB/Y006542/1 - 财政年份:2024
- 资助金额:
$ 15.89万 - 项目类别:
Research Grant
Canadian Alliance of Healthy Hearts and Minds: Dissecting the Pathways Linking Ectopic Adipose Tissue to Cognitive Dysfunction
加拿大健康心灵联盟:剖析异位脂肪组织与认知功能障碍之间的联系途径
- 批准号:
479570 - 财政年份:2023
- 资助金额:
$ 15.89万 - 项目类别:
Operating Grants
Determinants of Longitudinal Progression of Adipose Tissue Inflammation in Individuals at High-Risk for Type 2 Diabetes: Novel Insights from Metabolomic Profiling
2 型糖尿病高危个体脂肪组织炎症纵向进展的决定因素:代谢组学分析的新见解
- 批准号:
488898 - 财政年份:2023
- 资助金额:
$ 15.89万 - 项目类别:
Operating Grants
Activation of human brown adipose tissue using food ingredients that enhance the bioavailability of nitric oxide
使用增强一氧化氮生物利用度的食品成分激活人体棕色脂肪组织
- 批准号:
23H03323 - 财政年份:2023
- 资助金额:
$ 15.89万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of new lung regeneration therapies by elucidating the lung regeneration mechanism of adipose tissue-derived stem cells
通过阐明脂肪组织干细胞的肺再生机制开发新的肺再生疗法
- 批准号:
23K08293 - 财政年份:2023
- 资助金额:
$ 15.89万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A study on the role of brown adipose tissue in the development and maintenance of skeletal muscles
棕色脂肪组织在骨骼肌发育和维持中作用的研究
- 批准号:
23K19922 - 财政年份:2023
- 资助金额:
$ 15.89万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
Adipose Tissue T Cell Polarization and Metabolic Health in Persons Living with HIV
HIV 感染者的脂肪组织 T 细胞极化和代谢健康
- 批准号:
10619176 - 财政年份:2023
- 资助金额:
$ 15.89万 - 项目类别:
Estrogen Signaling in the Ventromedial Hypothalamus Modulates Adipose Tissue Metabolic Adaptation
下丘脑腹内侧区的雌激素信号调节脂肪组织代谢适应
- 批准号:
10604611 - 财政年份:2023
- 资助金额:
$ 15.89万 - 项目类别:
Obesity and Childhood Asthma: The Role of Adipose Tissue
肥胖和儿童哮喘:脂肪组织的作用
- 批准号:
10813753 - 财政年份:2023
- 资助金额:
$ 15.89万 - 项目类别: