GENETICS OF PCOS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本方案的总体目的是检验遗传因素导致胰腺细胞无法充分补偿多囊卵巢综合征（PCOS）胰岛素抵抗的假设。胰岛素抵抗是PCOS患者发生2型糖尿病的关键因素。我们发现，胰岛素分泌缺陷也在这一人群患糖尿病的易感性中起重要作用，并且一级亲属中的2型糖尿病史似乎定义了PCOS受试者中最严重的细胞功能缺陷。我们还发现，低剂量糖皮质激素给药可以作为一种药理学探针，检测亚临床缺陷的细胞功能，从而允许识别那些在发展糖尿病的最高风险。在本研究中，我们建议利用候选基因的方法来研究PCOS胰岛素分泌功能障碍的遗传基础。

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. The overall aim of this protocol is to test the hypothesis that genetic factors contribute to the failure of the pancreatic ¿-cell to adequately compensate for insulin resistance in polycystic ovary syndrome (PCOS). Insulin resistance is a key factor in the development of type 2 diabetes in PCOS. We have found that insulin secretory defects also play an important role in predisposing this population to diabetes and that a history of type 2 diabetes in a first-degree relative appears to define a subset of PCOS subjects with the most profound defects in ¿-cell function. We have also found that that low-dose glucocorticoid administration may act as a pharmacologic probe to detect subclinical defects in ¿-cell function, thus permitting identification of those at highest risk for developing diabetes. In the present studies we propose to utilize a candidate gene approach to study the genetic basis of insulin secretory dysfunction in PCOS.