PI-3-kinase mediated signaling by insulin and IGF-1

描述(由申请人提供)： 2型糖尿病严重影响数百万美国人的生活质量和寿命。2型糖尿病主要是由胰岛素引起的信号传导受损引起的。PI-3-激酶在胰岛素信号转导途径中起着至关重要的作用。这一研究项目将更好地确定PI-3-K转导胰岛素信号的机制。初步证据表明，胰岛素刺激PI3K移位到离散的细胞内位置，这与其他生长因子的反应截然不同。据推测，这种独特的亚细胞定位是胰岛素独特的信号效应的部分原因。这将通过定义胰岛素刺激的PI-3-激酶信号的亚细胞定位，控制这种定位的机制，以及这种定位的功能来进一步研究。人们期望对胰岛素信号通路的更好理解将有助于深入了解糖尿病的病理生理机制，并确定新的治疗方法的潜在靶点。 该项目还将对菲尔德博士的职业发展做出重大贡献。在刘易斯·坎特利博士和安妮·克利班斯基博士的指导下，这一职业发展奖有望将菲尔德博士培养成一名成功的独立临床医生兼科学家。

DESCRIPTION (provided by applicant): Type 2 diabetes mellitus seriously impacts on the quality of life and longevity of millions of Americans. Type 2 diabetes mellitus is caused primarily by impaired signaling by insulin. PI-3- kinase plays a crucial role in the insulin signaling pathway. This research project will better define the mechanism by which PI-3-kinase transduces the insulin signal. Preliminary evidence indicates that insulin stimulates the translocation of PI3K to discrete intracellular locations, quite distinct from the response to other growth factors. It is hypothesized that this distinct subcellular localization is partly responsible for the unique signaling effects of insulin. This will be investigated further by defining the subcellular localization of insulin-stimulated PI-3-kinase signaling, the mechanism governing this localization, and the function of this localization. It is expected that a better understanding of the signaling pathway utilized by insulin will provide insight into the pathophysiology of diabetes mellitus and identify potential targets for novel therapeutics. This project will also contribute significantly to the career development of Dr. Field. Under the mentorship of Dr. Lewis Cantley and Dr. Anne Klibanski this career development award is expected to foster Dr. Field's development into a successful independent clinician-scientist.