Insulin Modulates Parasympathetic Nerve Control of Lungs
胰岛素调节肺的副交感神经控制
基本信息
- 批准号:9233398
- 负责人:
- 金额:$ 46.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-15 至 2020-11-30
- 项目状态:已结题
- 来源:
- 关键词:1-Phosphatidylinositol 3-KinaseAcetylcholineAgonistAnimal ModelAntibodiesAsthmaBiguanidesBindingBlocking AntibodiesBronchoconstrictionClinical TrialsComputer AnalysisCost SavingsDataDietDrug TargetingFat-Restricted DietFunctional disorderGenetic TranscriptionHigh Fat DietHumanHypoglycemic AgentsImage AnalysisIncidenceInflammationInsulinInsulin ReceptorInsulin Signaling PathwayInsulin-Like-Growth Factor I ReceptorLungM2 proteinMeasuresMediatingMessenger RNAMetforminMethodsMitogen-Activated Protein Kinase KinasesModelingMolecularMuscarinic AntagonistsMuscarinic M2 ReceptorMuscarinic M3 ReceptorMuscarinicsNerveNeuronsNon obeseObesityOralPathway interactionsPatientsPeroxisome Proliferator-Activated ReceptorsPharmaceutical PreparationsPhenotypePhysiologicalPioglitazoneProtein IsoformsRattusResearchResistanceRoleSecond Messenger SystemsSeveritiesSignal PathwaySmooth MuscleStreptozocinStructure of parasympathetic ganglionTestingThree-Dimensional ImageTracheaTreatment Costairway hyperresponsivenessasthmaticinnovationmRNA ExpressionmRNA Transcript Degradationneuroblastoma cellnovel strategiespre-clinicalpreventprotein expressionreceptorreceptor expressionreceptor functionreceptor internalizationrespiratory smooth muscleresponse
项目摘要
Project Summary:
Obesity increases the incidence and severity of asthma, but an incomplete understanding of the molecular
mechanisms underlying obesity-related asthma make it difficult prevent and treat this phenotype.
Parasympathetic nerves mediate one mechanism of airway hyperreactivity. These nerves provide dominant
autonomic control of airway tone and release acetylcholine (ACh), which activates M3 muscarinic receptors on
airway smooth muscle, causing contraction and bronchoconstriction. ACh release is controlled by inhibitory M2
muscarinic receptors on these nerves. Thus, airway hyperreactivity results from decreased neuronal M2
receptor function and subsequent increased ACh release. Our preliminary data show that obesity is associated
with increased bronchoconstriction in response to parasympathetic nerve stimulation, with reduced neuronal M2
receptor function, and that these effects are mediated by insulin even in the absence of inflammation. Thus, our
hypothesis is that increased insulin, as seen in obesity, binds to insulin receptors on airway
parasympathetic nerves resulting in airway hyperreactivity by reducing M2 muscarinic function on
parasympathetic nerves (thus increasing ACh release). We propose to test how insulin reduces M2
receptor expression and function, identify which insulin receptor and signaling pathways mediate neuronal M2
dysfunction and test whether manipulating insulin (with diet, oral anti-glycemic drugs and with an insulin binding
antibody) protects M2 receptor function and inhibits obesity induced airway hyperreactivity. This research is
significant because it has the potential to explain why obese patients with increased insulin, are more prone to
asthma and identify novel strategies, including control of insulin, and M3 selective muscarinic antagonists, that
may treat obesity-related asthma.
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(0)
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ALLISON Deborah FRYER其他文献
ALLISON Deborah FRYER的其他文献
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{{ truncateString('ALLISON Deborah FRYER', 18)}}的其他基金
Insulin increases nerve-mediated bronchoconstriction in obesity-related asthma
胰岛素增加肥胖相关哮喘中神经介导的支气管收缩
- 批准号:
10587344 - 财政年份:2022
- 资助金额:
$ 46.25万 - 项目类别:
Oregon Clinical and Translational Research Institute TL1 Program
俄勒冈临床和转化研究所 TL1 项目
- 批准号:
9514380 - 财政年份:2017
- 资助金额:
$ 46.25万 - 项目类别:
Oregon Clinical and Translational Research Institute TL1 Program
俄勒冈临床和转化研究所 TL1 项目
- 批准号:
10197247 - 财政年份:2017
- 资助金额:
$ 46.25万 - 项目类别:
Role of macrophages in organophosphorus pesticide-induced airway hyperreactivity
巨噬细胞在有机磷农药引起的气道高反应性中的作用
- 批准号:
8106431 - 财政年份:2010
- 资助金额:
$ 46.25万 - 项目类别:
Role of macrophages in organophosphorus pesticide-induced airway hyperreactivity
巨噬细胞在有机磷农药引起的气道高反应性中的作用
- 批准号:
8663694 - 财政年份:2010
- 资助金额:
$ 46.25万 - 项目类别:
Role of macrophages in organophosphorus pesticide-induced airway hyperreactivity
巨噬细胞在有机磷农药引起的气道高反应性中的作用
- 批准号:
8462262 - 财政年份:2010
- 资助金额:
$ 46.25万 - 项目类别:
Role of macrophages in organophosphorus pesticide-induced airway hyperreactivity
巨噬细胞在有机磷农药引起的气道高反应性中的作用
- 批准号:
8008728 - 财政年份:2010
- 资助金额:
$ 46.25万 - 项目类别:
Role of macrophages in organophosphorus pesticide-induced airway hyperreactivity
巨噬细胞在有机磷农药引起的气道高反应性中的作用
- 批准号:
8272650 - 财政年份:2010
- 资助金额:
$ 46.25万 - 项目类别:
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