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: 7056650
• 负责人: HEIDI A TISSENBAUM
• 金额: $ 31.72万
• 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/7056650
• 关键词: Caenorhabditis elegans; JUN kinase; acetylcholine; biological signal transduction; diabetes mellitus genetics; disease /disorder onset; dopamine; gamma aminobutyrate; gene mutation; genetic regulation; glutamates; immunoprecipitation; insulin receptor; insulin sensitivity /resistance; lipid metabolism; longevity; microarray technology; molecular pathology; neurotransmitter transport; noninsulin dependent diabetes mellitus; obesity; octopamine; serotonin

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）：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巨大增加。使个人患有II型糖尿病的第二个因素是年龄。 随着个人的年龄，他们更有可能患上II型糖尿病。尽管肥胖，衰老和II型糖尿病的发作之间的联系很明显，但分子细节仍有待确定。 该项目的长期目标是揭示分子机制，该机制解释了胰岛素样信号，衰老和脂肪储存之间的联系，以便在人类中更好地控制II型糖尿病。在这里，我们使用线虫秀丽隐杆线虫作为模型系统，因为胰岛素信号通路在人类和秀丽隐杆线虫之间是高度保守的，并且线虫已成为研究胰岛素信号传导的出色系统。在此提案中，我们试图确定与秀丽隐杆线虫胰岛素样信号通路相连的新基因和新途径，以确定该信号网络如何控制寿命和脂肪存储。拟议的研究将检验我们的假设，即胰岛素样信号通路中的突变会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连接。我们的具体目的是：（1）确定DAF-2上游神经递质信号传导的作用； （2）定义TUB-1基因在调节寿命和脂肪储存中的作用；和 （3）确定JNK控制寿命和脂肪存储的机制。虽然每个目标都是 独立，研究了胰岛素样信号通路的不同部分，在每个步骤中，我们都将分析突变对寿命和脂肪储存的影响。我们有信心，了解寿命跨度，脂肪储存和类似胰岛素的信号之间的分子连接将与哺乳动物系统相关，因为所有基因和途径似乎都保守。