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

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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.