INSULIN ACTION IN THE POLYCYSTIC OVARY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。多囊卵巢综合征（PCOS）是绝经前妇女最常见的内分泌疾病之一，影响了5-10%的绝经前妇女。它是激素相关性不孕的主要原因。患有多囊卵巢综合征的女性男性激素水平升高，月经不规律。他们经常有胰岛素抵抗，使患2型糖尿病的风险增加了7倍（成人发病）。多囊卵巢综合征是一种遗传性疾病。我们最近发现了一个遗传标记，D19S884的等位基因8 (A8)，它位于胰岛素受体附近的第19染色体上。该标记与多囊卵巢综合征的生殖表型显著相关。所有受试者的雄激素，胰岛素，血糖和血脂水平都将被测量。将对多囊卵巢综合征相关的代谢和脂质异常进行强化检查。将比较A8+和A8- PCOS女性以及对照组中胰岛素分泌和作用、肥胖风险以及对喂养过量和喂养不足的代谢反应的差异。PCOS女性的A8+男性一级男性亲属将接受检查，看他们是否有与A8+ PCOS女性相似的代谢改变。通过抽吸获得的腹部脂肪和活检获得的大腿中部肌肉的小样本将在胰岛素敏感性的体外研究中进行检查。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5-10% of this population. It is the leading cause of hormonally-related infertility. Women with PCOS have elevated male hormone levels and irregular periods. They frequently have insulin resistance, conferring a seven-fold increased risk for type 2 diabetes mellitus (adult onset). PCOS is an inherited disorder. We recently discovered a genetic marker, allele 8 (A8) of D19S884, which is located on chromosome 19 near the insulin receptor. This marker is significantly associated with the PCOS reproductive phenotype. Androgen, insulin, glucose and lipid levels will be measured in all subjects. Intensive testing to examine the metabolic and lipid abnormalities associated with PCOS will be performed. Differences in insulin secretion and action, obesity risk, and metabolic response to over- and underfeeding will be compared in A8+ and A8- PCOS women as well as controls. A8+ male first-degree male relatives of PCOS women will be examined to see if they have similar metabolic alterations identified in A8+ PCOS women. Small samples of abdominal fat obtained by aspiration and mid-thigh muscle obtained by biopsy will be examined in in vitro studies of insulin sensitivity.