PI-3-Kinase Signaling over Physiologic Time-Scales/Response to Insulin or IGF-1

PI-3-激酶信号转导在生理时间尺度上/对胰岛素或 IGF-1 的反应

• 批准号: 7127535
• 负责人: SETH J FIELD
• 金额: $ 7.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127535
• 关键词: adipocytes; animal tissue; binding proteins; biological signal transduction; enzyme activity; enzyme mechanism; hormone regulation /control mechanism; insulin; insulinlike growth factor; molecular /cellular imaging; noninsulin dependent diabetes mellitus; phosphatidylinositol 3 kinase; platelet derived growth factor; protein localization; protein structure function

DESCRIPTION (provided by applicant): If awarded, this R03 grant would provide supplemental funding during the final two years of the applicant's K08 award. The additional funding would provide crucial resources, such as technical assistance, that would enhance the applicant's ability to compete for further grant support and would facilitate establishment as an independent researcher. Type 2 diabetes mellitus affects 18 million Americans, seriously impacting on their quality of life and longevity. Type 2 diabetes mellitus is caused primarily by impaired signaling by insulin. The signaling pathways that are activated within the first ten to fifteen minutes of hormone treatment by insulin or the highly related growth factor IGF-1 have been studied extensively. Surprisingly little is known about membrane-proximal signaling events over longer, more physiologically relevant, time-courses or in response to falling insulin levels. This grant application proposes to study the behavior of the crucial PI-3-kinase pathway over long time-courses in response to rising or falling insulin or IGF-1 levels using powerful imaging techniques that we developed during our research funded by the associated K08 award to track the PI-3-kinase pathway. We also propose a screen to identify novel targets of Ptdlns(3,4,5)P3 as potentially novel elements in the insulin/IGF-1 signaling pathway. We expect that improved understanding of the insulin signaling pathway will eventually lead to improved treatment strategies for insulin resistance and type II diabetes mellitus.

描述（由申请人提供）： 如果授予，这个R 03赠款将提供补充资金在申请人的K 08奖的最后两年。额外的资金将提供关键资源，如技术援助，这将提高申请人争取进一步赠款支持的能力，并将有助于成为独立研究人员。 2型糖尿病影响着1800万美国人，严重影响他们的生活质量和寿命。2型糖尿病主要由胰岛素信号传导受损引起。胰岛素或高度相关的生长因子IGF-1在激素治疗的前10至15分钟内激活的信号通路已被广泛研究。令人惊讶的是，人们对更长时间、更具生理相关性的时间过程或响应胰岛素水平下降的近膜信号事件知之甚少。这项拨款申请建议研究关键的PI-3-激酶通路在长时间内的行为，以应对胰岛素或IGF-1水平的上升或下降，使用强大的成像技术，我们在相关的K 08奖资助的研究中开发，以跟踪PI-3-激酶通路。我们还提出了一个筛选，以确定新的目标Ptdlns（3，4，5）P3作为潜在的新元素在胰岛素/IGF-1信号通路。我们期望对胰岛素信号通路的进一步了解将最终导致改善胰岛素抵抗和II型糖尿病的治疗策略。