PHYSIOLOGICAL CHARACTERIZATION OF INDIVIDUALS WITH VARIANTS IN THE HNF-4A PRO

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 研究人员通过一项横断面设计，发现HNF-4A的P2(B细胞)启动子区域的变异与胰岛素抵抗的B细胞补偿减少之间存在关联。该研究采用横断面设计，研究对象为既往患有妊娠期糖尿病的墨西哥裔美国女性及其家庭成员。本建议的主要目的是通过口服和静脉葡萄糖耐量试验和分级葡萄糖输注来确定其中一个变异是否与胰岛素和葡萄糖之间的异常剂量-反应关系和/或随时间推移而加速的B细胞功能丧失有关。预计这些信息将帮助我们更多地了解HNF-4A如何参与糖尿病的发展，以及它可能与糖尿病相关的机制。

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 investigators have found an association between variants in the P2 (B-cell) promoter region of HNF-4A and reduced B-cell compensation for insulin resistance using a cross sectional design in Mexican American women with prior GDM and their family members. The main purpose of the present proposal is to determine whether one of these variants is associated with abnormal dose-response relationships between insulin and glucose and/or accelerated loss of B-cell function over time using oral and intravenous glucose tolerance tests and graded glucose infusions. It is anticipated that this information will help us understand more about how HNF-4A is involved in the development of diabetes and also the mechanisms by which it may be associated with diabetes.