Mechanisms of Prediabetic States in Obstructive Sleep Apnea

阻塞性睡眠呼吸暂停的糖尿病前期状态机制

基本信息

  • 批准号:
    10439458
  • 负责人:
  • 金额:
    $ 77.16万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-07-15 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Substantial clinical and experimental evidence indicates that obstructive sleep apnea (OSA) is associated with impaired glucose metabolism. Our laboratory has demonstrated that treatment of OSA by all-night continuous positive airway pressure (CPAP) improves insulin sensitivity and glucose tolerance in prediabetes. To date, the mechanisms by which OSA impairs glucose metabolism remain unclear. It is widely recognized that OSA patients have increased sympathetic activity, which is a potent stimulator of adipose tissue lipolysis leading to increased release of free fatty acids (FFA) into the systemic circulation. FFAs are a major source of energy for the skeletal muscle, which is the tissue that accounts for the majority of insulin-stimulated glucose uptake. Extensive research has demonstrated that ectopic lipid accumulation in the skeletal muscle is one of the key determinants of insulin resistance. We therefore hypothesized is that increased adipose tissue lipolysis (i.e. excess FFA delivery) induced by OSA impairs metabolism in the skeletal muscle, leading to insulin resistance and glucose intolerance. We hypothesize that these impairments occur in part through mitochondrial dysfunction, as mitochondria are important in glucose and fatty acid oxidation, and are highly abundant in the skeletal muscle. Specifically, we will determine whether OSA leads to insulin resistance and glucose intolerance through impairments of cellular metabolism resulting in incomplete substrate utilization and ectopic lipid accumulation in the skeletal muscle (Aim 1) and determine to what extent the metabolic impairments in OSA are explained by increased adipose tissue lipolysis and excess FFA release (Aim 2). To address these aims, we propose to study OSA patients with prediabetes under three in-laboratory conditions in a randomized cross-over design: untreated condition (OSA), treated condition (CPAP), untreated but pharmacologically suppressed lipolysis condition (FFA-suppressed). We will perform whole body and cellular assessments under each study condition. Glucose metabolism will be assessed during both fasting and postprandial states using stable isotope tracers. In muscle tissue, we will assess mitochondrial oxygen consumption, reactive oxygen species, glucose and fat oxidation, fatty acid transport to mitochondria, ectopic accumulation of lipid metabolites, and insulin signaling. The proposed work will be the first to assess cellular bioenergetics (i.e. mitochondrial function) in OSA patients and seeks to determine whether cellular metabolic impairments in the skeletal muscle contribute to insulin resistance and glucose intolerance in OSA, and whether these impairments are occurring in the presence of excess FFA delivery (i.e. by overwhelming mitochondrial capacity) and/or are primary (occurring without excess FFA presence). The mechanistic insights that are expected to be gained from the proposed work will help identify novel targets for risk prediction and/or treatment of metabolic impairments in OSA beyond CPAP.
项目总结/文摘

项目成果

期刊论文数量(0)
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Esra Tasali其他文献

Esra Tasali的其他文献

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{{ truncateString('Esra Tasali', 18)}}的其他基金

Sleep Extension: A Novel Intervention for Weight Loss in Young Adults
延长睡眠:年轻人减肥的新干预措施
  • 批准号:
    10753226
  • 财政年份:
    2023
  • 资助金额:
    $ 77.16万
  • 项目类别:
Technology-Supported Treatment of Sleep Apnea in Prediabetes
糖尿病前期睡眠呼吸暂停的技术支持治疗
  • 批准号:
    9762470
  • 财政年份:
    2019
  • 资助金额:
    $ 77.16万
  • 项目类别:
Mechanisms of Prediabetic States in Obstructive Sleep Apnea
阻塞性睡眠呼吸暂停的糖尿病前期状态机制
  • 批准号:
    10222768
  • 财政年份:
    2019
  • 资助金额:
    $ 77.16万
  • 项目类别:
Technology-Supported Treatment of Sleep Apnea in Prediabetes
糖尿病前期睡眠呼吸暂停的技术支持治疗
  • 批准号:
    10226277
  • 财政年份:
    2019
  • 资助金额:
    $ 77.16万
  • 项目类别:
Mechanisms of Prediabetic States in Obstructive Sleep Apnea
阻塞性睡眠呼吸暂停的糖尿病前期状态机制
  • 批准号:
    9973169
  • 财政年份:
    2019
  • 资助金额:
    $ 77.16万
  • 项目类别:
Technology-Supported Treatment of Sleep Apnea in Prediabetes
糖尿病前期睡眠呼吸暂停的技术支持治疗
  • 批准号:
    10677837
  • 财政年份:
    2019
  • 资助金额:
    $ 77.16万
  • 项目类别:
Technology-Supported Treatment of Sleep Apnea in Prediabetes
糖尿病前期睡眠呼吸暂停的技术支持治疗
  • 批准号:
    10459449
  • 财政年份:
    2019
  • 资助金额:
    $ 77.16万
  • 项目类别:
Technology-Supported Treatment of Sleep Apnea in Prediabetes
糖尿病前期睡眠呼吸暂停的技术支持治疗
  • 批准号:
    9980894
  • 财政年份:
    2019
  • 资助金额:
    $ 77.16万
  • 项目类别:
Technology-Supported Treatment of Sleep Apnea in Prediabetes
糖尿病前期睡眠呼吸暂停的技术支持治疗
  • 批准号:
    10886362
  • 财政年份:
    2019
  • 资助金额:
    $ 77.16万
  • 项目类别:
Mechanisms of Prediabetic States in Obstructive Sleep Apnea
阻塞性睡眠呼吸暂停的糖尿病前期状态机制
  • 批准号:
    10674545
  • 财政年份:
    2019
  • 资助金额:
    $ 77.16万
  • 项目类别:

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