Life span, Fat Storage and Insulin-like Signaling

寿命、脂肪储存和类胰岛素信号传导

• 批准号: 8729556
• 负责人: HEIDI A TISSENBAUM
• 金额: $ 32.41万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8729556
• 关键词: Address; Animals; Biochemical; Caenorhabditis elegans; Development; Disease; Fatty acid glycerol esters; Gene Expression; Genes; Genetic; Insulin; Insulin-Like Growth Factor I; Longevity; Longitudinal Studies; Mammals; Molecular Genetics; Nematoda; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathway interactions; Phosphoric Monoester Hydrolases; Phosphotransferases; Phylogeny; Protein Serine/Threonine Phosphatase; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; RNA Interference; Reagent; Regulation; Resources; Signal Pathway; Signal Transduction; Site; System; Testing; Threonine; gene function; insulin signaling; novel

DESCRIPTION (provided by applicant): In mammals, there appears to be an intimate linkage between insulin signaling, life span, and fat storage. Reductions in insulin signaling promote excess fat storage, and obesity can result in insulin insensitivity. We use the nematode C. elegans to address our hypothesis that multiple conserved signaling pathways including TGF-2 and TOR, modulate insulin/IGF-1 signaling to coordinately regulate life span and fat storage. C. elegans possess an insulin/IGF-1 signaling pathway that is well conserved across species. Modulating this pathway leads to changes in life span and fat storage. Therefore, worms are an excellent system to determine how multiple pathways influence the insulin/IGF-1 signaling pathway for life span and fat storage regulation. To address our hypothesis we will perform the following three specific aims (1) We will dissect the cross talk between the TGF-2 and insulin/IGF-1 pathways (2) We will dissect the cross talk the TOR and insulin/IGF-1 signaling (3) We will identify phosphatases that regulate the Insulin/IGF-1 signaling pathway to modulate life span and fat storage. These phosphatases may regulate the insulin/IGF-1 signaling pathway or one of the multiple conserved pathways that couple the insulin/IGF-1 pathway. Over the long term, these studies should help to understand the complexities associated with diseases such as Type II diabetes.

描述（由申请人提供）：在哺乳动物中，胰岛素信号传导，寿命和脂肪储存之间似乎存在着亲密的联系。胰岛素信号的减少会促进过多的脂肪储存，肥胖会导致胰岛素不敏感。我们使用线虫秀丽隐杆线虫来解决我们的假设，即多个保守的信号通路在内，包括TGF-2和TOR，调节胰岛素/IGF-1信号传导以协调调节寿命和脂肪存储。秀丽隐杆线虫具有胰岛素/IGF-1信号传导途径，该途径在整个物种之间都充分保守。调节此途径会导致寿命和脂肪存储的变化。因此，蠕虫是确定多种途径如何影响胰岛素/IGF-1信号传导途径的绝佳系统。为了解决我们的假设，我们将执行以下三个具体目标（1）我们将在TGF-2和胰岛素/IGF-1途径之间进行剖析（2）我们将剖析横串交谈TOR和胰岛素/IGF-1信号传导（3），我们将识别调节胰岛素/IGF-1信号途径的磷酸化酶以调节寿命和脂肪的寿命。这些磷酸酶可能调节胰岛素/IGF-1信号通路或将胰岛素/IGF-1途径的多个保守途径之一。从长远来看，这些研究应有助于了解与II型糖尿病等疾病相关的复杂性。