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: 8284360
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8284360
• 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; public health relevance

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. PUBLIC HEALTH RELEVANCE: The insulin/IGF-1 signaling pathway is conserved across phylogeny. In this proposal, we dissect how additional conserved signaling pathways couple with the insulin/IGF-1 signaling pathway to cooperatively regulate life span and fat storage.

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密切联系。胰岛素信号的减少会促进过多的脂肪储存，而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，即包括 TGF-2 和 TOR 在内的多种保守信号通路可调节胰岛素/IGF-1 信号传导以协调调节寿命和脂肪储存。秀丽隐杆线虫拥有在不同物种间都高度保守的胰岛素/IGF-1 信号通路。调节该途径会导致寿命和脂肪储存的变化。因此，线虫是一个很好的系统，可以确定多种途径如何影响胰岛素/IGF-1信号通路，从而实现寿命和脂肪储存调节。为了解决我们的假设，我们将实现以下三个具体目标 (1) 我们将剖析 TGF-2 和胰岛素/IGF-1 通路之间的串扰 (2) 我们将剖析 TOR 和胰岛素/IGF-1 通路之间的串扰信号传导 (3) 我们将鉴定调节胰岛素/IGF-1 信号传导途径的磷酸酶，从而调节寿命和脂肪储存。这些磷酸酶可能调节胰岛素/IGF-1 信号传导途径或耦合胰岛素/IGF-1 途径的多个保守途径之一。从长远来看，这些研究应该有助于理解与二型糖尿病等疾病相关的复杂性。 公共卫生相关性：胰岛素/IGF-1 信号通路在整个系统发育过程中都是保守的。在本提案中，我们剖析了额外的保守信号通路如何与胰岛素/IGF-1信号通路相结合，共同调节寿命和脂肪储存。