Life span, fat storage and insulin-like signaling

寿命、脂肪储存和胰岛素样信号传导

• 批准号: 7227419
• 负责人: HEIDI A TISSENBAUM
• 金额: $ 30.82万
• 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 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7227419
• 关键词: 1-Phosphatidylinositol 3-Kinase; Acetylcholine; Age; Age of Onset; Aging; Biochemical; Biochemical Genetics; Biological Assay; Biological Models; Caenorhabditis elegans; Calcium Signaling; Co-Immunoprecipitations; Coupled; Data; Disruption; Fatty acid glycerol esters; Genes; Goals; Homologous Gene; Human; Immunoprecipitation; Individual; Insulin; Insulin Receptor; Insulin Signaling Pathway; Insulin-Like-Growth Factor I Receptor; JNK-activating protein kinase; Lead; Longevity; MAPK8 gene; Microarray Analysis; Molecular; Molecular Genetics; Mutation; Nematoda; Neurons; Neurotransmitters; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Obesity; Open Reading Frames; Orthologous Gene; Output; Pathway interactions; Pattern; Personal Satisfaction; Phosphotransferases; Predisposing Factor; Prevalence; Process; Protein Overexpression; Regulation; Research Personnel; Role; Serotonin; Signal Pathway; Signal Transduction; System; Testing; Yeasts; forkhead protein; insulin signaling; mutant; programs; promoter; yeast two hybrid system

DESCRIPTION (provided by applicant): The prevalence of Type II diabetes is rapidly increasing in the US. This is in part due to the huge increase in the number of obese people. A second factor that predisposes individuals to Type II diabetes is age. As individuals age, they become more likely to develop Type II diabetes. Although the connection between obesity, aging, and the onset of Type II diabetes is clear, the molecular details remain to be determined. The long-term goal of this project is to uncover the molecular mechanism that explains the connection between insulin-like signaling, aging and fat storage, so that Type II diabetes and can be better controlled in humans. Here, we use the nematode, C. elegans, as our model system since the insulin signaling pathway is highly conserved between humans and C. elegans, and nematodes have emerged as an excellent system to study insulin signaling. In this proposal, we seek to identify new genes and new pathways coupled to the C. elegans insulin-like signaling pathway to determine how this signaling network controls both life span and fat storage. The proposed studies will test our hypothesis that mutations in the insulin-like signaling pathway lead to changes in life span and fat storage because these processes have an underlying molecular connection. Our specific aims are to: (1) Identify the role of neurotransmitter signaling upstream of daf-2; (2) Define the role of the tub-1 gene in regulation of life span and fat storage; and (3) Determine the mechanism for JNK control of life span and fat storage. Although each aim is independent, investigating a different part of the insulin-like signaling pathway, at each step we will be analyzing the effects of mutations on life span and fat storage. We are confident that understanding the molecular connection between life span, fat storage, and insulin-like signaling will have relevance to mammalian systems because all of the genes and pathways appear conserved.

描述（由申请人提供）：在美国，II型糖尿病的患病率正在迅速增加。这部分是由于肥胖人数的大幅增加。第二个因素，易患II型糖尿病的个人是年龄。 随着年龄的增长，他们更容易患上II型糖尿病。虽然肥胖、衰老和II型糖尿病发病之间的联系是明确的，但分子细节仍有待确定。 该项目的长期目标是揭示解释胰岛素样信号传导，衰老和脂肪储存之间联系的分子机制，以便在人类中更好地控制II型糖尿病。在这里，我们使用线虫，C。elegans作为我们的模型系统，因为胰岛素信号通路在人类和C.线虫和线虫已经成为研究胰岛素信号传导的极好系统。在这个建议中，我们试图确定新的基因和新的途径耦合到C。elegans胰岛素样信号通路，以确定该信号网络如何控制寿命和脂肪储存。拟议的研究将验证我们的假设，即胰岛素样信号通路的突变导致寿命和脂肪储存的变化，因为这些过程具有潜在的分子联系。我们的具体目标是：（1）确定daf-2上游神经递质信号传导的作用;（2）确定tub-1基因在寿命和脂肪储存调节中的作用;和 (3)确定JNK控制寿命和脂肪储存的机制。虽然每一个目标 独立，调查胰岛素样信号通路的不同部分，在每一步，我们将分析突变对寿命和脂肪储存的影响。我们相信，了解寿命、脂肪储存和胰岛素样信号传导之间的分子联系将与哺乳动物系统相关，因为所有基因和途径似乎都是保守的。