Vesicle Translocation and the Metabolic Syndrome

囊泡易位和代谢综合征

基本信息

  • 批准号:
    10592402
  • 负责人:
  • 金额:
    $ 51.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-04-01 至 2026-02-28
  • 项目状态:
    未结题

项目摘要

Abstract The regulation of glucose homeostasis is a complex process, which is disrupted in disease states such as type 2 diabetes. Insulin is the primary hormone that regulates glucose homeostasis. Insulin stimulates glucose uptake in muscle and fat by mobilizing intracellular vesicles containing GLUT4 glucose transporters, which fuse and insert GLUT4 at the cell surface. Impairment of this process results in insulin resistance and contributes to the development of diabetes. Therefore, to understand the pathogenesis of metabolic disease, it is necessary to understand the molecular mechanisms that control GLUT4 trafficking, and to understand how this trafficking is modulated by insulin and disrupted in insulin resistance. Previous work identified the TUG protein as a major regulator of GLUT4 trafficking and glucose uptake in muscle and fat cells. The data support a model in which TUG mediates the intracellular retention of GLUT4 in specific vesicles within unstimulated cells. Insulin triggers TUG endoproteolytic cleavage to mobilize these vesicles to the cell surface. TUG cleavage coordinates glucose uptake with other physiologic effects, resulting from the action of proteins that co-traffic with GLUT4, as well as from action of the TUG C-terminal product to modulate gene expression. In insulin resistant individuals, impairment of this mechanism may contribute to the metabolic syndrome and obesity. Yet, it remains unknown how this mechanism is affected in insulin resistance, whether attenuated TUG cleavage causes insulin resistance in muscle, or whether TUG cleavage participates in exercise-stimulated glucose uptake. As well, the molecular mechanisms by which intact TUG retains GLUT4 in an insulin- responsive pool of vesicles are not understood. To address these questions, two Aims will be undertaken. Aim 1 will characterize insulin resistance and glucose homeostasis in mice with muscle-specific disruption of TUG or of TUG endoproteolytic cleavage, and will study the potential role of this pathway in exercise-induced glucose uptake. Aim 2 will study molecular mechanisms by which TUG traps GLUT4-containing vesicles in an insulin-responsive pool, and by which this process may be altered in insulin-resistant states. We anticipate that, together, these studies will result in an improved understanding of glucose metabolism and energy expenditure, with implications for the prevention and treatment of diabetes and the metabolic syndrome.
摘要 葡萄糖稳态的调节是一个复杂的过程,其在疾病状态中被破坏,例如 2糖尿病.胰岛素是调节葡萄糖稳态的主要激素。胰岛素刺激葡萄糖 通过动员含有GLUT 4葡萄糖转运蛋白的细胞内囊泡, 并在细胞表面插入GLUT 4。这一过程的损害导致胰岛素抵抗,并有助于 糖尿病的发展。因此,了解代谢性疾病的发病机制, 了解控制GLUT 4运输的分子机制,并了解这种运输如何 受胰岛素调节并破坏胰岛素抵抗。以前的工作确定TUG蛋白是一种 肌肉和脂肪细胞中GLUT 4运输和葡萄糖摄取的主要调节剂。数据支持一个模型, 该TUG介导GLUT 4在未刺激细胞内的特定囊泡中的细胞内滞留。胰岛素 触发TUG内切蛋白水解切割以将这些囊泡移动到细胞表面。TUG裂解 协调葡萄糖摄取与其他生理效应,这是由共同运输的蛋白质的作用引起的 与GLUT 4,以及从TUG C-末端产物的作用,以调节基因表达。胰岛素 抵抗个体,该机制的损伤可能导致代谢综合征和肥胖。 然而,这一机制在胰岛素抵抗中是如何受到影响的,无论是减弱TUG, 切割导致肌肉中的胰岛素抵抗,或者TUG切割是否参与运动刺激的 葡萄糖摄取同样,完整的TUG将GLUT 4保留在胰岛素受体中的分子机制, 囊泡的响应池尚不清楚。为了解决这些问题,将采取两个目标。 目的1将描述肌肉特异性破坏胰岛素抵抗和葡萄糖稳态的小鼠, TUG或TUG内蛋白水解裂解,并将研究这一途径在运动诱导的 葡萄糖摄取目的2将研究TUG捕获含GLUT 4的囊泡的分子机制, 胰岛素应答池,并且通过其可以在胰岛素抵抗状态下改变该过程。我们预计 总之,这些研究将导致对葡萄糖代谢和能量的更好理解, 这一研究结果表明,糖尿病和代谢综合征的预防和治疗是一个非常重要的问题。

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 }}

JONATHAN BOGAN其他文献

JONATHAN BOGAN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('JONATHAN BOGAN', 18)}}的其他基金

Vesicle Translocation and the Metabolic Syndrome
囊泡易位和代谢综合征
  • 批准号:
    10452851
  • 财政年份:
    2022
  • 资助金额:
    $ 51.62万
  • 项目类别:
Vesicle Translocation and the Metabolic Syndrome
囊泡易位和代谢综合征
  • 批准号:
    10161017
  • 财政年份:
    2020
  • 资助金额:
    $ 51.62万
  • 项目类别:
Regulation of insulin sensitivity by TUG acetylation
通过 TUG 乙酰化调节胰岛素敏感性
  • 批准号:
    8516944
  • 财政年份:
    2012
  • 资助金额:
    $ 51.62万
  • 项目类别:
Regulation of insulin sensitivity by TUG acetylation
通过 TUG 乙酰化调节胰岛素敏感性
  • 批准号:
    8386145
  • 财政年份:
    2012
  • 资助金额:
    $ 51.62万
  • 项目类别:
Vesicle Translocation and the Metabolic Syndrome
囊泡易位和代谢综合征
  • 批准号:
    9116816
  • 财政年份:
    2012
  • 资助金额:
    $ 51.62万
  • 项目类别:
Vesicle translocation and the metabolic syndrome
囊泡易位和代谢综合征
  • 批准号:
    8297209
  • 财政年份:
    2012
  • 资助金额:
    $ 51.62万
  • 项目类别:
Vesicle translocation and the metabolic syndrome
囊泡易位和代谢综合征
  • 批准号:
    8518317
  • 财政年份:
    2012
  • 资助金额:
    $ 51.62万
  • 项目类别:
Insulin stimulated ubiquitin-like modification
胰岛素刺激的泛素样修饰
  • 批准号:
    7260014
  • 财政年份:
    2007
  • 资助金额:
    $ 51.62万
  • 项目类别:
Insulin stimulated ubiquitin-like modification
胰岛素刺激的泛素样修饰
  • 批准号:
    7631186
  • 财政年份:
    2007
  • 资助金额:
    $ 51.62万
  • 项目类别:
Insulin stimulated ubiquitin-like modification
胰岛素刺激的泛素样修饰
  • 批准号:
    8066936
  • 财政年份:
    2007
  • 资助金额:
    $ 51.62万
  • 项目类别:

相似国自然基金

相似海外基金

New development of cellular regeneration therapy in jaw bone using stem cells derived from adipocytes jaw bone
利用颌骨脂肪细胞来源的干细胞进行颌骨细胞再生治疗的新进展
  • 批准号:
    23K16058
  • 财政年份:
    2023
  • 资助金额:
    $ 51.62万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
A novel mechanism of insulin resistance mediated by uric acid metabolism in adipocytes
脂肪细胞尿酸代谢介导胰岛素抵抗的新机制
  • 批准号:
    23K10969
  • 财政年份:
    2023
  • 资助金额:
    $ 51.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Hypertrophic adipocytes as biophysical mediators of breast cancer progression
肥大脂肪细胞作为乳腺癌进展的生物物理介质
  • 批准号:
    10751284
  • 财政年份:
    2023
  • 资助金额:
    $ 51.62万
  • 项目类别:
Development of adipocytes for gene therapy that avoids cellular stress due to overexpression of therapeutic proteins
开发用于基因治疗的脂肪细胞,避免因治疗蛋白过度表达而造成的细胞应激
  • 批准号:
    23H03065
  • 财政年份:
    2023
  • 资助金额:
    $ 51.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Functional analysis of bitter taste receptors in adipocytes and hepatocytes
脂肪细胞和肝细胞中苦味受体的功能分析
  • 批准号:
    23K05107
  • 财政年份:
    2023
  • 资助金额:
    $ 51.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Elucidation of mechanisms for conversion of adipocytes to cancer-associated fibroblasts in osteosarcoma microenvironment
阐明骨肉瘤微环境中脂肪细胞转化为癌症相关成纤维细胞的机制
  • 批准号:
    23K19518
  • 财政年份:
    2023
  • 资助金额:
    $ 51.62万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Study on UCP-1 independent metabolic regulation by brown adipocytes
棕色脂肪细胞对UCP-1独立代谢调节的研究
  • 批准号:
    23K18303
  • 财政年份:
    2023
  • 资助金额:
    $ 51.62万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
NKA/CD36 signaling in adipocytes promotes oxidative stress and drives chronic inflammation in atherosclerosis
脂肪细胞中的 NKA/CD36 信号传导促进氧化应激并驱动动脉粥样硬化的慢性炎症
  • 批准号:
    10655793
  • 财政年份:
    2023
  • 资助金额:
    $ 51.62万
  • 项目类别:
The mechanisms of the signal transduction from brown adipocytes to afferent neurons and its significance.
棕色脂肪细胞向传入神经元的信号转导机制及其意义。
  • 批准号:
    23K05594
  • 财政年份:
    2023
  • 资助金额:
    $ 51.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Characterizing breast cancer invasion and proliferation when co-aggregated with adipocytes in multicellular spheroids created with a custom bioreactor to augment cell-cell connectivity.
当与多细胞球体中的脂肪细胞共聚集时,表征乳腺癌的侵袭和增殖,该多细胞球体是用定制生物反应器创建的,以增强细胞间的连接。
  • 批准号:
    10334113
  • 财政年份:
    2022
  • 资助金额:
    $ 51.62万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了