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Polycystic Ovary Syndrome: Role of Insulin Resistance

多囊卵巢综合症：胰岛素抵抗的作用

基本信息

批准号：
7618017
负责人：
JOHN E NESTLER
金额：
$ 15.45万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-04-01 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7618017
关键词：
Affect Anovulation Arts Award Biochemical Chronic Clinical Investigator Clinical Research Clinical Services Compensatory Hyperinsulinemia Development Diazoxide Disease Female of child bearing age Funding Grant Growth Health Hyperandrogenism Hyperinsulinism Inositol Insulin Insulin Resistance Intravenous Life Mediator of activation protein Medicine Mentors Mentorship Metabolic Clearance Rate Metabolic syndrome Methodology Modeling Non obese OGTT Obesity Pioglitazone Play Polycystic Ovary Syndrome Renal clearance function Research Research Personnel Research Training Risk Role Sampling Series Testing Time Training United States National Institutes of Health Universities Virginia Woman career design improved inositolphosphoglycan insulin mediators insulin sensitivity insulin tolerance islet medical schools patient oriented patient oriented research professor translational study

项目摘要

DESCRIPTION (provided by applicant): This competitive renewal application for a K24 Mid-Career Investigator Award in Patient-Oriented Research is to provide continued support for the development of Dr. John E. Nestler as a clinical investigator and, most importantly, as a research mentor. Dr. Nestler is Professor of Medicine at Virginia Commonwealth University's Medical College of Virginia, and has been a productive patient-oriented investigator whose research focus has been the pathophysiologic role of insulin resistance in the polycystic ovary syndrome (PCOS), a disorder that affects 6-10% of women of childbearing age. Dr. Nestler has an established track record of mentorship of young clinical investigators, and has been highly successful in providing research training to young investigators during the 4 year tenure of the active K24 grant. The broad long-term objective of Dr. Nestler's studies has been to conduct both mechanistic and translational studies exploring the role of insulin resistance in PCOS. The specific studies proposed in this application, which are currently funded by an NIH R01 grant, are designed to determine: 1) if decreasing circulating insulin directly by inhibition of islet insulin release with diazoxide in obese women with PCOS (i) decreases renal clearance of D-chiro-inositol (uCIDCI) and (ii) increases the circulating concentration of DCI; 2) if decreasing circulating insulin indirectly, by improving insulin sensitivity with pioglitazone, in obese women with PCOS (i) decreases uCIDCI, (ii) increases the circulating concentration of DCI, and (iii) enhances the insulin-stimulated release of the putative DCI-inositolphosphoglycan mediator during an OGTT [oral glucose tolerance test]; and 3) if acutely increasing circulating insulin in non obese women with PCOS increases uCIDCI and/or the metabolic clearance rate of DCI. These studies will be conducted on the General Clinical Research Center (GCRC) using state of the art methodologies, such as the modified minimal model FSIVGTT [frequently-sampled intravenous insulin tolerance] to determine insulin sensitivity. The K24 renewal will allow Dr. Nestler to continue his increased mentorship of young investigators and to enhance his personal growth as a clinical investigator. It will do so by continuing to provide Dr. Nestler with increased protected time and to maintain decreases in administrative duties and clinical service responsibilities. As a result of the K24 renewal, Dr. Nestler will be able to devote 75-85% effort to research, personal development in clinical research, and, most importantly, the training and mentorship of young investigators.

描述（由申请人提供）：这项以患者为导向的研究中的 K24 职业生涯中期研究者奖的竞争性续展申请旨在为 John E. Nestler 博士作为临床研究者，最重要的是作为研究导师的发展提供持续的支持。 Nestler 博士是弗吉尼亚联邦大学弗吉尼亚医学院的医学教授，一直是一位富有成效的以患者为中心的研究人员，其研究重点是胰岛素抵抗在多囊卵巢综合征 (PCOS) 中的病理生理作用，这种疾病影响 6-10% 的育龄妇女。 Nestler 博士在指导年轻临床研究人员方面有着良好的记录，并且在活跃的 K24 资助的 4 年任期内，在为年轻研究人员提供研究培训方面取得了巨大成功。 Nestler 博士研究的广泛长期目标是进行机制研究和转化研究，探索胰岛素抵抗在 PCOS 中的作用。本申请中提出的具体研究目前由 NIH R01 拨款资助，旨在确定：1) 是否通过用二氮嗪抑制患有 PCOS 的肥胖女性的胰岛胰岛素释放来直接减少循环胰岛素 (i) 降低 D-手性肌醇 (uCIDCI) 的肾脏清除率和 (ii) 增加 DCI 的循环浓度； 2) 如果通过吡格列酮改善胰岛素敏感性间接降低循环胰岛素，则肥胖 PCOS 女性 (i) 降低 uCIDCI，(ii) 增加 DCI 循环浓度，以及 (iii) 在 OGTT [口服葡萄糖耐量]期间增强胰岛素刺激的推定 DCI-肌醇磷酸聚糖介质的释放测试]; 3) 如果患有 PCOS 的非肥胖女性急剧增加循环胰岛素会增加 uCIDCI 和/或 DCI 的代谢清除率。这些研究将在综合临床研究中心 (GCRC) 上进行，采用最先进的方法，例如用于确定胰岛素敏感性的改良最小模型 FSIVGTT（频繁采样静脉注射胰岛素耐受性）。 K24 续约将使 Nestler 博士能够继续加强对年轻研究者的指导，并促进他作为临床研究者的个人成长。为此，它将继续为 Nestler 医生提供更多的保护时间，并继续减少行政职责和临床服务职责。 K24 更新后，Nestler 博士将能够将 75-85% 的精力投入到研究、临床研究中的个人发展，以及最重要的是年轻研究人员的培训和指导。