Function and Regulation of Islet-associated Macrophages in Obesity and Diabetes
Function and Regulation of Islet-associated Macrophages in Obesity and Diabetes
批准号:
8617401
负责人:
David L Morris
金额:
$10.9万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-09-05 至 2017-06-30
关键词:
Adipose tissueApoptosisAutoimmune ProcessAwardBeta CellBiologyCell LineCell physiologyCellsChemotaxisChronicCoculture TechniquesCommitComplementDataDefectDevelopmentDiabetes MellitusExhibitsFlow CytometryFoundationsFunctional disorderFutureGene Expression ProfilingGlucoseGlucose IntoleranceGoalsHousingHumanImaging TechniquesImmuneImmunophenotypingIndianaInfiltrationInflammationInflammatoryInsulinInsulin ResistanceInsulin-Dependent Diabetes MellitusInterdisciplinary StudyIslets of LangerhansLaboratoriesLeadLeftLeukocytesLiverMacrophage ActivationMediatingMentorshipMetabolicMetabolic DiseasesMetabolic stressMetabolismModelingMolecularMusMuscleNon-Insulin-Dependent Diabetes MellitusObese MiceObesityPathogenesisPatientsPediatric ResearchPhenotypePhysiologyPopulationRegulationResearchResearch PersonnelResearch TrainingRiskRodent ModelRoleSecretory CellStaining methodStainsSystemTestingTherapeuticTissuesTrainingUniversitiesWorkcareercareer developmentcytokinedesigndriving forceendoplasmic reticulum stressimpaired glucose toleranceimprovedinnovationinsulin secretionisletmacrophagemedical schoolsmonocytemouse modelprogramspublic health relevanceresearch studyresponseskills
中文摘要
项目总结
英文摘要
Project Summary
The applicant's career goal is to develop a multidisciplinary research program focused on defining how
inflammation contributes to the development of metabolic disease. Emerging data from the past decade has
revealed that obesity-induced metabolic inflammation is a key driving force in the pathogenesis of Type 2
diabetes mellitus (T2DM). In the adipose tissue, liver, and muscle, it is well recognized that obesity leads to
progressive infiltration of activated pro-inflammatory macrophages and other leukocytes that act in concert to
induce insulin resistance and metabolic dysfunction. At present, relatively little is known about whether and
how islet-associated macrophages contribute to islet inflammation, glucose intolerance, and beta cell
dysfunction in T2DM. Furthermore, the phenotype, function, and regulation of islet-associated macrophages
during the progression of metabolic inflammation and T2DM have yet to be fully defined, leaving critical gaps in
our understanding of the pathogenesis of this serious metabolic disease. The central hypothesis of this
application is that obesity-induced metabolic stress causes the accumulation of pro-inflammatory macrophages
within the islet that exacerbate beta cell dysfunction in T2DM. To test this hypothesis and to begin to uncover
the role of islet-associated macrophages in the progression of T2DM, three Specific Aims are proposed. Aim 1
will determine the immunophenotype and inflammatory profile of islet-associated macrophages during the
progression of glucose intolerance and T2DM in mouse models. Aim 2 will define the interplay between beta
cell endoplasmic reticulum (ER) stress and recruitment and activation of islet-associated macrophages. Aim 3
will investigate the effects of pro-inflammatory macrophages on beta cell secretory function in obesity and
T2DM. The diverse experimental approaches outlined in the research plan will allow the applicant to broaden
his diabetes expertise by developing new proficiencies and complementary skill sets in the assessment of beta
cell function in mouse models, isolated islets, and commonly used beta cell lines. The applicant will benefit
from training in the Basic Diabetes Research Group within the Herman B Wells Center for Pediatric Research
at the Indiana University School of Medicine, which houses five laboratories that are committed to
understanding the molecular mechanisms that lead to the development of all forms of diabetes mellitus. This
new training in islet biology will complement the applicant's previous training in physiology, metabolism, and
obesity-induced inflammation. A diverse team of established investigators will oversee the applicant's career
development during the award period by contributing intellectually to his research training, providing
mentorship, and offering career advice.
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Function and Regulation of Islet-associated Macrophages in Obesity and Diabetes
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批准号:9028604
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项目类别:
-
资助金额:$0.1万
-
财政年份:2013
-
负责人:David L Morris
-
依托单位:
Function and Regulation of Islet-associated Macrophages in Obesity and Diabetes
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批准号:8730650
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项目类别:
-
资助金额:$10.9万
-
财政年份:2013
-
负责人:David L Morris
-
依托单位:
Function and Regulation of Islet-associated Macrophages in Obesity and Diabetes
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批准号:8877510
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项目类别:
-
资助金额:$10.9万
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财政年份:2013
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负责人:David L Morris
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依托单位:
Role of CD40 in Obesity-Induced Adipose Tissue Inflammation & Insulin Resistance
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批准号:8124157
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项目类别:
-
资助金额:$4.84万
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财政年份:2011
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负责人:David L Morris
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依托单位:
Role of CD40 in Obesity-Induced Adipose Tissue Inflammation & Insulin Resistance
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批准号:8265988
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项目类别:
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资助金额:$5.22万
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财政年份:2011
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负责人:David L Morris
-
依托单位:
Role of CD40 in Obesity-Induced Adipose Tissue Inflammation & Insulin Resistance
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批准号:8472491
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项目类别:
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资助金额:$3.3万
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财政年份:2011
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负责人:David L Morris
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依托单位:
SH2-B Regulation of Hypothalamic AgRP/NPY Neurons
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批准号:7431719
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项目类别:
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资助金额:$3.35万
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财政年份:2006
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负责人:David L Morris
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依托单位:
SH2-B Regulation of Hypothalamic AgRP/NPY Neurons
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批准号:7263859
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项目类别:
-
资助金额:$3.31万
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财政年份:2006
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负责人:David L Morris
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依托单位:
SH2-B Regulation of Hypothalamic AgRP/NPY Neurons
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批准号:7154925
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项目类别:
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资助金额:$3.27万
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财政年份:2006
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负责人:David L Morris
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依托单位:
国内基金
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