Life span, fat storage and insulin-like signaling

描述（由申请人提供）：在美国，II型糖尿病的患病率正在迅速上升。这在一定程度上是由于肥胖人数的大幅增加。第二个使人易患二型糖尿病的因素是年龄。随着年龄的增长，人们更有可能患上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，但其分子细节仍有待确定。该项目的长期目标是揭示胰岛素样信号、衰老和脂肪储存之间联系的分子机制，从而更好地控制人类的II型糖尿病。在这里，我们使用线虫秀丽隐杆线虫作为我们的模型系统，因为胰岛素信号通路在人类和秀丽隐杆线虫之间高度保守，线虫已经成为研究胰岛素信号传导的一个很好的系统。在本提案中，我们寻求识别与秀丽隐杆线虫胰岛素样信号通路耦合的新基因和新途径，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上游神经递质信号的作用；(2)明确tub-1基因在调节寿命和脂肪储存中的作用；和

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.