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

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)
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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:
NRSA Training Core
NRSA 培训核心
  • 批准号:
    10693309
  • 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:
NRSA Training Core
NRSA 培训核心
  • 批准号:
    10675197
  • 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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