A novel autophagy gene beclin 2 in the prevention of type 2 diabetes and obesity

新型自噬基因 beclin 2 预防 2 型糖尿病和肥胖

基本信息

  • 批准号:
    8989093
  • 负责人:
  • 金额:
    $ 23.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-01-01 至 2016-12-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract The objective of this K99/R00 Pathway to Independence Award application is to study the functions and mechanisms of a novel autophagy gene beclin 2 in the prevention of type 2 diabetes and obesity. Type 2 diabetes is a metabolic disorder characterized by the inability of pancreatic � cells to compensate for body insulin resistance, often accompanied by obesity. However, the pathogenesis of obesity-related type 2 diabetes is incompletely understood. Recently, both activation of autophagy and downregulation of the cannabinoid receptor 1 (CB1R) signaling have been implicated in preventing diabetes/obesity. During my postdoctoral training, I discovered and cloned a novel mammalian-specific autophagy gene belonging to the Beclin (coiled-coil, myosin-like BCL2-interacting protein) family, beclin 2, and my preliminary data showed that the disruption of beclin 2 has striking effects on autophagy, CB1R trafficking and turnover, and metabolic regulation. In this application, I will focus on studying the mechanisms of Beclin 2 in autophagy and CB1R trafficking/signaling in vitro and in vivo: Aim 1 characterizes the molecular mechanism(s) of Beclin 2 in the regulation of autophagy, through biochemical methods and structure-function studies of protein-protein interactions of Beclin 2; Aim 2 investigates the function and mechanisms by which Beclin 2 regulates CB1R degradation and signaling, and study whether this function of Beclin 2 interrelates with its role in autophagy; and Aim 3 studies the in vivo functions of Beclin 2 in maintaining insulin sensitivity and preventing obesity in response to regular diet and high-fat diet challenge, using a knockout mouse model (beclin 2-/-) and a conditional knockout mouse model (beclin 2flox/flox) that I have recently generated. These studies will shed light on the role and cellular mechanisms of autophagy in metabolic regulation, and help understand the impact of therapeutic manipulation of autophagy in metabolic diseases. Under the auspices of the University of Texas Southwestern Medical Center, I will be mentored by internationally recognized leaders in the fields of autophagy and metabolism, which will aid the transition of my research career toward an independent investigator position.
项目总结/文摘

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Activating Autophagy by Aerobic Exercise in Mice.
Exercise induces autophagy in peripheral tissues and in the brain.
  • DOI:
    10.4161/auto.21327
  • 发表时间:
    2012-10
  • 期刊:
  • 影响因子:
    13.3
  • 作者:
    He C;Sumpter R Jr;Levine B
  • 通讯作者:
    Levine B
Regulation of Exercise-Induced Autophagy in Skeletal Muscle.
  • DOI:
    10.1007/s40139-017-0135-9
  • 发表时间:
    2017-06
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Rocchi A;He C
  • 通讯作者:
    He C
Emerging roles of autophagy in metabolism and metabolic disorders.
  • DOI:
    10.1007/s11515-015-1354-2
  • 发表时间:
    2015-04
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Rocchi A;He C
  • 通讯作者:
    He C
Regulation of plasma membrane receptors by a new autophagy-related BECN/Beclin family member.
一种新的自噬相关 BECN/Beclin 家族成员对质膜受体的调节。
  • DOI:
    10.4161/auto.29414
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    13.3
  • 作者:
    Zhang,Weiran;He,Congcong
  • 通讯作者:
    He,Congcong
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Congcong He其他文献

Congcong He的其他文献

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{{ truncateString('Congcong He', 18)}}的其他基金

Autophagic regulation of cocaine abuse
可卡因滥用的自噬调节
  • 批准号:
    10838802
  • 财政年份:
    2022
  • 资助金额:
    $ 23.6万
  • 项目类别:
Autophagic regulation of cocaine abuse
可卡因滥用的自噬调节
  • 批准号:
    10682457
  • 财政年份:
    2022
  • 资助金额:
    $ 23.6万
  • 项目类别:
Autophagic regulation of cocaine abuse
可卡因滥用的自噬调节
  • 批准号:
    10503559
  • 财政年份:
    2022
  • 资助金额:
    $ 23.6万
  • 项目类别:
Autophagy-facilitated secretion in metabolic maintenance
自噬促进代谢维持中的分泌
  • 批准号:
    10367132
  • 财政年份:
    2021
  • 资助金额:
    $ 23.6万
  • 项目类别:
Autophagy-facilitated secretion in metabolic maintenance
自噬促进代谢维持中的分泌
  • 批准号:
    10490364
  • 财政年份:
    2021
  • 资助金额:
    $ 23.6万
  • 项目类别:
Autophagy-facilitated secretion in metabolic maintenance
自噬促进代谢维持中的分泌
  • 批准号:
    10665778
  • 财政年份:
    2021
  • 资助金额:
    $ 23.6万
  • 项目类别:
Mechanism of autophagy activation in exercise-induced anti-diabetic benefits
自噬激活在运动引起的抗糖尿病益处中的机制
  • 批准号:
    10522769
  • 财政年份:
    2017
  • 资助金额:
    $ 23.6万
  • 项目类别:
Mechanism of autophagy activation in exercise-induced anti-diabetic benefits
自噬激活在运动引起的抗糖尿病益处中的机制
  • 批准号:
    10704114
  • 财政年份:
    2017
  • 资助金额:
    $ 23.6万
  • 项目类别:
A novel autophagy gene beclin 2 in the prevention of type 2 diabetes and obesity
新型自噬基因 beclin 2 预防 2 型糖尿病和肥胖
  • 批准号:
    8774357
  • 财政年份:
    2014
  • 资助金额:
    $ 23.6万
  • 项目类别:
A novel autophagy gene beclin 2 in the prevention of type 2 diabetes and obesity
新型自噬基因 beclin 2 预防 2 型糖尿病和肥胖
  • 批准号:
    8538967
  • 财政年份:
    2012
  • 资助金额:
    $ 23.6万
  • 项目类别:

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在男性和女性健康志愿者中进行的一项随机双盲安慰剂对照 1 期 SAD 研究,旨在评估 ABCA1 激动剂 CS6253 的安全性、药代动力学和短暂生物标志物变化
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  • 项目类别:
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研究阿片类激动剂治疗 OUD 患者结果的机制:解开睡眠和昼夜节律对渴望和情绪调节的影响
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一种基于纳米抗体的新型激动剂重定向检查点 (ARC) 分子 aPD1-Fc-OX40L,用于癌症免疫治疗
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  • 项目类别:
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