Incretins and Nutrient induced Plasticity

肠促胰素和营养诱导的可塑性

基本信息

  • 批准号:
    RGPIN-2017-05996
  • 负责人:
  • 金额:
    $ 1.68万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2019
  • 资助国家:
    加拿大
  • 起止时间:
    2019-01-01 至 2020-12-31
  • 项目状态:
    已结题

项目摘要

Incretins and Nutrient Induced Plasticity******The intestine is not a passive conduit but a large, dynamic organ which adjusts to large variations in both nutrient supply and energy demand. The structure of the mucosa undergoes robust adaptation as cellular processes including epithelial cell proliferation, apoptosis and differentiation may be downregulated with nutrient deprivation and recovered upon nutrient ingestion. As the gut is an energetically demanding organ, maintaining sufficient work capacity for nutrient absorption while offsetting metabolic cost is vital. Two incretin hormone peptides are secreted from enteroendocrine L cells and K cells respectively, glucagon like peptide 1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) very rapidly post-prandially. GLP-1 and GIP each signal through a distinct G-protein coupled receptor, the GLP-1R and GIPR respectively and are classically thought to target the islet to increase glucose-stimulated insulin secretion. However, the incretin receptors are expressed throughout the gastrointestinal tract and the enteroendocrine cells which secrete GLP-1 and GIP are in direct contact with nutrients in the intestinal lumen, the microvasculature and nervous system making them ideally situated to mediate the highly adaptive response from a fasted to fed state. This proposal aims to identify and define novel signaling pathways through which the incretin hormones GIP and GLP-1 dynamically regulate the structure and function of the intestinal tract in response to ingested nutrients.******Hypothesis: The gut derived incretin hormones, GLP-1 and GIP mediate intestinal nutrient-induced plasticity.***Objectives: In order to define the mechanisms underlying the role of the incretin hormones for mediating nutrient induced plasticity, a number of key experiments are required. In Wildtype (WT) and Double Incretin Receptor Knock Out mice (DIRKO) littermate controls exposed to fasting or post-prandial conditions we will determine if: (a) morphological composition of the gut changes appropriately with feeding, (b) cell growth and differentiation of the epithelium, (c) the effect of incretin signaling on digestion and nutrient absorption, (d) apoptosis and proliferation of the gut epithelium, (e) if the expression levels and protein levels of key effectors required for fasting or refeeding blocked in mice in which the GLP-1R and GIPR have been deleted. ******The applicant has significant expertise with all of the techniques included in this proposal; therefore trainees will acquire a number of complementary and sophisticated tools/approaches for isolating cells and appropriate use of animals to apply to their future research programs. ******Expected Results and Relevance: We anticipate identifying a critical role for GIPR and GLP-1R signaling in mediating the adaptation of the small intestine to nutrient intake. ************R
肠促胰岛素和营养诱导的可塑性 * 肠不是被动的管道,而是一个大型的动态器官,可以适应营养供应和能量需求的巨大变化。粘膜的结构经历了强大的适应,因为细胞过程包括上皮细胞增殖、凋亡和分化可能随着营养剥夺而下调,并在营养摄入后恢复。由于肠道是一个需要能量的器官,因此保持足够的营养吸收工作能力,同时抵消代谢成本至关重要。胰高血糖素样肽1(GLP-1)和葡萄糖依赖性促胰岛素多肽(GIP)分别由肠内分泌L细胞和K细胞在餐后非常迅速地分泌。GLP-1和GIP各自通过不同的G蛋白偶联受体(分别为GLP-1 R和GIPR)发出信号,传统上认为其靶向胰岛以增加葡萄糖刺激的胰岛素分泌。然而,肠降血糖素受体在整个胃肠道中表达,并且分泌GLP-1和GIP的肠内分泌细胞与肠腔、微血管系统和神经系统中的营养物质直接接触,使得它们理想地处于介导从禁食到进食状态的高度适应性反应的位置。 该提案旨在确定和定义新的信号通路,通过这些信号通路,肠促胰岛素激素GIP和GLP-1动态调节肠道的结构和功能,以响应摄入的营养素。假设:肠源性肠促胰岛素激素GLP-1和GIP介导肠营养诱导的可塑性。目的:为了确定肠促胰岛素激素介导营养诱导的可塑性的作用机制,需要进行一些关键实验。在暴露于空腹或餐后条件的野生型(WT)和双肠促胰岛素受体敲除小鼠(DIRKO)同窝对照中,我们将确定是否:(a)肠的形态组成随着进食而适当地改变,(B)上皮细胞的生长和分化,(c)肠促胰岛素信号传导对消化和营养吸收的影响,(d)肠上皮细胞的凋亡和增殖,(e)在GLP-1 R和GIPR缺失的小鼠中,禁食或再喂养所需的关键效应物的表达水平和蛋白质水平是否被阻断。** 申请人对本提案中包含的所有技术都具有重要的专业知识;因此,学员将获得一些用于分离细胞和适当使用动物的补充和复杂的工具/方法,以应用于他们未来的研究计划。** 预期结果和相关性:我们预期确定GIPR和GLP-1 R信号在介导小肠适应营养摄入方面的关键作用。我的天啊

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Mulvihill, Erin其他文献

Mulvihill, Erin的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Mulvihill, Erin', 18)}}的其他基金

Incretins and Nutrient induced Plasticity
肠促胰岛素和营养诱导的可塑性
  • 批准号:
    RGPIN-2017-05996
  • 财政年份:
    2022
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Discovery Grants Program - Individual
Incretins and Nutrient induced Plasticity
肠促胰素和营养诱导的可塑性
  • 批准号:
    RGPIN-2017-05996
  • 财政年份:
    2021
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Discovery Grants Program - Individual
Incretins and Nutrient induced Plasticity
肠促胰素和营养诱导的可塑性
  • 批准号:
    RGPIN-2017-05996
  • 财政年份:
    2020
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Discovery Grants Program - Individual
Incretins and Nutrient induced Plasticity
肠促胰岛素和营养诱导的可塑性
  • 批准号:
    RGPIN-2017-05996
  • 财政年份:
    2018
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Discovery Grants Program - Individual
Incretins and Nutrient induced Plasticity
肠促胰岛素和营养诱导的可塑性
  • 批准号:
    RGPIN-2017-05996
  • 财政年份:
    2017
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Discovery Grants Program - Individual

相似海外基金

Role of skeletal muscle IPMK in nutrient metabolism and exercise
骨骼肌IPMK在营养代谢和运动中的作用
  • 批准号:
    10639073
  • 财政年份:
    2023
  • 资助金额:
    $ 1.68万
  • 项目类别:
Molecular mechanisms of pathogenesis induced by endophytic bacteria of Brassica species in a nutrient-dependent manner
芸苔属内生细菌以营养依赖性方式诱导发病的分子机制
  • 批准号:
    23KF0025
  • 财政年份:
    2023
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Cellular domancy induced by low-nutrient environment
低营养环境诱导的细胞休眠
  • 批准号:
    23K05010
  • 财政年份:
    2023
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Placental Insulin Signaling and mTOR Nutrient-Sensing Programming of Offspring Metabolic Health
胎盘胰岛素信号传导和 mTOR 营养感应编程对后代代谢健康的影响
  • 批准号:
    10625938
  • 财政年份:
    2022
  • 资助金额:
    $ 1.68万
  • 项目类别:
Unconventional regulation of mTORC1 signaling by inositol phosphate: implications for nutrient-induced premature aging
磷酸肌醇对 mTORC1 信号传导的非常规调节:对营养诱导的过早衰老的影响
  • 批准号:
    10372324
  • 财政年份:
    2022
  • 资助金额:
    $ 1.68万
  • 项目类别:
Impact of beech water and nutrient stress induced by understory degradation on soil biodiversity and ecosystem function
林下退化引起的山毛榉水和养分胁迫对土壤生物多样性和生态系统功能的影响
  • 批准号:
    22H03793
  • 财政年份:
    2022
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Elucidating how nutrient-limiting soil conditions drive plant-induced weathering processes under a changing climate
阐明在气候变化下限制养分的土壤条件如何驱动植物引起的风化过程
  • 批准号:
    RGPIN-2022-04512
  • 财政年份:
    2022
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Discovery Grants Program - Individual
Incretins and Nutrient induced Plasticity
肠促胰岛素和营养诱导的可塑性
  • 批准号:
    RGPIN-2017-05996
  • 财政年份:
    2022
  • 资助金额:
    $ 1.68万
  • 项目类别:
    Discovery Grants Program - Individual
Unconventional regulation of mTORC1 signaling by inositol phosphate: implications for nutrient-induced premature aging
磷酸肌醇对 mTORC1 信号传导的非常规调节:对营养诱导的过早衰老的影响
  • 批准号:
    10772905
  • 财政年份:
    2022
  • 资助金额:
    $ 1.68万
  • 项目类别:
Microbiota-dependent Epigenetic Regulation of Circadian Rhythms in Nutrient Uptake and Energy Homeostasis
营养吸收和能量稳态中昼夜节律的微生物依赖表观遗传调节
  • 批准号:
    10323791
  • 财政年份:
    2021
  • 资助金额:
    $ 1.68万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了