Intramuscular Triglyceride in Impaired Glucose Tolerance

描述(由申请人提供)： 候选人：Leigh Perreault，医学博士，董事会认证的内科医生和内分泌学家，在流行病学、基础科学和临床研究方面拥有过去十年的经验。她最近的工作是研究急性运动后胰岛素作用的性别差异，这项工作得到了内分泌研究员基金会的支持。该项目产生了新的和重要的差异，为与胰岛素作用相关的运动燃料代谢领域的继续研究奠定了基础。毫无保留地，最突出的职业目标是让候选人作为一名独立的内科科学家取得卓越的成就。以患者为导向的导师研究职业发展奖将提供必要的培训，以追求和实现这一目标。 职业发展：培训计划包括两个主要内容：1)通过当地导师获得大量新的研究技能，以及三个预定的学徒时间；2)教育活动，包括正式的课堂工作，以及出席和参加国家会议、当地研讨会和期刊俱乐部，以及一对一的导师互动。 研究计划：拟议项目的总体目标是描绘骨骼肌中胰岛素抵抗发展过程中的性别差异。了解这些差异将有助于扩大我们对胰岛素抵抗本身的病理生理学的了解，并有助于胰岛素增敏治疗的靶向。一般的假设是，糖耐量受损(IGT)的男性和女性通过不同的机制在骨骼肌中产生胰岛素抵抗。具体地说，我们假设这是通过降低女性的氧化能力和男性的过氧化体增殖物激活受体(PPAR)α(及其靶基因)的作用来实现的。此外，女性的运动训练和男性的贝特治疗将减轻这些错乱。最先进的技术人员将会被彻底摧毁。环境：应聘者的培训环境特殊。这位导师是罗伯特·H·埃克尔医学博士，是胰岛素作用和底物摄取领域的国际专家，此外，他也是一位久经考验的导师。这位共同导师克里斯托弗·A·德索萨博士是学术研究领域的一颗冉冉升起的新星，拥有运动和底物使用方面的专业知识。总体而言，导师、合作者和机构承诺都很出色。

DESCRIPTION (provided by applicant): Candidate: The candidate, Leigh Perreault, MD, is a board-certified internist and endocrinologist with experience in epidemiologic, basic science, and clinical research spanning the past decade. Her most recent work examining gender differences in insulin action following acute exercise was supported by an Award from the Endocrine Fellows Foundation. This project has yielded novel and important differences which have layed the foundation for continuing research in the area exercise fuel metabolism as it pertains to insulin action. Without reservation, the most outstanding career goal is for the candidate to achieve excellence as an independent physician-scientist. The Mentored Patient-Oriented Research Career Development Award would provide the necessary training to pursue and achieve this goal. Career Development: The training plan consists of two primary elements: 1) the acquistion of an impressive number of new research skills via the local mentors as well as three scheduled apprenticeships away; and 2) educational activities, including formal classroom work, as well as attendance and participation in national meetings, local seminars and journal clubs, and one-on-one mentor interactions. Research Plan: The overall aim of the proposed project is to delineate gender differences in the development of insulin resistance in skeletal muscle. Understanding such differences would help expand our knowledge of the pathophysiology of insulin resistance itself, as well as aid in the targeting of insulin sensitizing therapy. The general hypothesis is that men and women with impaired glucose tolerance (IGT) develop insulin resistance in skeletal muscle through different mechanisms. Specifically, we hypothesize that this occurs via decreased oxidative capacity in women, and decreased action of peroxisome proliferatoractivated receptor (PPAR) alpha (and its target genes) in men. Furthermore, exercise training in women, and fibrate therapy in men, will attenuate these derangements. State-of-the-art tecnhiques will be imployed. Environment: The environment for the candidate's training is exceptional. The mentor, Robert H. Eckel, MD, is an international expert in the area of insulin action and substrate uptake and, furthermore, is a proven mentor. The co-mentor, Christopher A. DeSouza, PhD, is a rising star in academic research with expertise in exercise and substrate use. Collectively, the mentors, collaborators, and institutional commitment excels.