Repurposing estrogens to improve pancreatic islet transplantation
Repurposing estrogens to improve pancreatic islet transplantation
批准号:
9185114
负责人:
Franck Mauvais-Jarvis
金额:
$36.73万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-07-01 至 2020-06-30
关键词:
5&apos-AMP-activated protein kinaseAcuteAgonistAllelesAnabolismApoptosisBeta CellBlood flowCellsChronicCollaborationsDataDevelopmentDiabetic mouseEndothelial CellsEngraftmentEstradiolEstrogen Receptor alphaEstrogen Receptor betaEstrogen ReceptorsEstrogensFailureFemaleFosteringFoundationsGPER geneGlucoseGoalsGrantHormonesHumanHypoxiaInsulinInsulin-Dependent Diabetes MellitusIslets of Langerhans TransplantationKnowledgeLaboratoriesMediatingMembraneMetabolismMolecularMusNOS3 geneNon-Insulin-Dependent Diabetes MellitusNuclearOutcomePathway interactionsPerformancePregnancyPropertyQualifyingReagentResearchRodent ModelRoleTherapeuticTissuesTransplantationUnited States National Institutes of HealthVEGFA geneVascular Endothelial Growth FactorsVascularizationVasodilationXenograft procedurebasecellular targetingdefined contributionhypoxia inducible factor 1improvedimproved outcomein vivoisletmouse modelnovelnovel strategiespreventprograms
中文摘要
摘要。
英文摘要
ABSTRACT.
The goal of this application is to use a mouse model to elucidate the mechanisms by which estrogen action, by
way of the estrogen receptor(ER)s, improves islet oxygenation, revascularization and functional mass during
pancreatic islet transplantation (PIT). Improving PIT outcome in type 1 diabetes (T1D) is a major goal of the
NIH. We must explore new, simple and safe therapeutic approaches to suppress islet apoptosis while
promoting islet oxygenation and revascularization in the immediate post-transplant period. Our laboratory was
the first to show that the female hormone 17β-estradiol (E2) protects islet β-cells from apoptosis via estrogen
receptors and in human islets. Our new preliminary data demonstrates that E2 enhances islet oxygenation,
revascularization and functional mass during PIT. We need to identify the actual cellular targets and molecular
pathways used by ERs to promote these actions. The specific aims of this application are to 1) Elucidate the
role ERs activation in graft β-cells to islet engraftment using mice with conditional null allele of ERs in these
cells (βERKO). We will explore a novel paradigm in which paradigm that ERα activation in graft β-cells
programs islet metabolism by way of AMP-activated protein kinase (AMPK) and away from hypoxia-inducible
factor-1 (HIF1) to improve islet performance during hypoxia. 2) Define the contribution of ERs activation in
recipient endothelial cells to islet engraftment using mice with conditional null allele of ERs in these cells
(VENERKO). We will explore a novel concept in which ERα activation in recipient mouse endothelial cells
promotes acute vasodilation and oxygenation via endothelial nitric oxide synthase (eNOS) and delayed
revascularization by way of vascular endothelial growth factor-A (VEGF-A).
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Role of the Androgen Receptor in Insulin Secretion in the Male
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批准号:10488954
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财政年份:2023
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依托单位:
The role of the androgen receptor in insulin secretion
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财政年份:2017
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The role of the androgen receptor in insulin secretion
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批准号:10045938
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财政年份:2017
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依托单位:
Targeting the estrogen receptor-ÃÂÃÂÃÂÃÂÃÂÃÂÃÂñ to protect functional ÃÂÃÂÃÂÃÂÃÂÃÂÃÂò-cell mass in women
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批准号:10217788
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财政年份:2007
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依托单位:
Targeting the estrogen receptor-α to protect functional β-cell mass in women
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批准号:10202562
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资助金额:$36.93万
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财政年份:2007
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负责人:Franck Mauvais-Jarvis
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依托单位:
Targeting Estrogen Receptors to Protect Functional Beta-cell Mass in Diabetes
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批准号:8545806
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项目类别:
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资助金额:$33.44万
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财政年份:2007
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负责人:Franck Mauvais-Jarvis
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依托单位:
Role of estrogen receptors in pancreatic beta-cell survival and insulin secretion
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批准号:7615652
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项目类别:
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资助金额:$27.38万
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财政年份:2007
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负责人:Franck Mauvais-Jarvis
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依托单位:
Role of estrogen receptors in pancreatic beta-cell survival and insulin secretion
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批准号:7787369
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项目类别:
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资助金额:$4.89万
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财政年份:2007
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负责人:Franck Mauvais-Jarvis
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依托单位:
Role of estrogen receptors in pancreatic beta-cell survival and insulin secretion
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批准号:8054720
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项目类别:
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资助金额:$27.79万
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财政年份:2007
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负责人:Franck Mauvais-Jarvis
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依托单位:
Role of estrogen receptors in pancreatic beta-cell survival and insulin secretion
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批准号:7408547
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项目类别:
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资助金额:$27.38万
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财政年份:2007
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负责人:Franck Mauvais-Jarvis
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依托单位:
Targeting Estrogen Receptors to Protect Functional Beta-cell Mass in Diabetes
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批准号:8438117
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项目类别:
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资助金额:$35.61万
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财政年份:2007
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负责人:Franck Mauvais-Jarvis
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依托单位:
Targeting Estrogen Receptors to Protect Functional Beta-cell Mass in Diabetes
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批准号:8730619
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项目类别:
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资助金额:$34.67万
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财政年份:2007
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负责人:Franck Mauvais-Jarvis
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依托单位:
Role of estrogen receptors in pancreatic beta-cell survival and insulin secretion
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批准号:7268242
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项目类别:
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资助金额:$27.94万
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财政年份:2007
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负责人:Franck Mauvais-Jarvis
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依托单位:
Estrogen receptor signaling in diabetes prevention
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批准号:6950054
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项目类别:
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资助金额:$15.0万
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财政年份:2004
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负责人:Franck Mauvais-Jarvis
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依托单位:
Estrogen receptor signaling in diabetes prevention
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批准号:6849526
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项目类别:
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资助金额:$15.0万
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财政年份:2004
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负责人:Franck Mauvais-Jarvis
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依托单位:
海外基金