PHARMACOGENETICS OF PRO 12ALA PPAR-GAMMA-2

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。本方案的目的是确定为什么有些人对噻唑烷二酮类（一类抗糖尿病药物）反应不佳。这些药物通过提高身体对胰岛素的敏感性来起作用。将根据受试者的基因型招募受试者，因为认为特定变体（Pro 12 Ala PPAR-gamma-2）可能导致对这些药物的反应减弱。将招募糖耐量受损（糖尿病的前兆）受试者，并接受罗格列酮（一种噻唑烷二酮）治疗。在罗格列酮治疗12周之前和之后，将测试胰岛素敏感性，包括葡萄糖摄取和脂解抑制（脂肪分解）。同样，将在治疗前后研究脂肪和肌肉中的基因表达。该方案以12周的教学性体重管理计划结束。

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 purpose of this protocol is to determine why some individuals do not respond well to thiazolidinediones, a class of antidiabetic drugs. These drugs work by improving the sensitivity of the body to insulin. Subjects will be recruited on the basis of their genotype, as it is believed that a particular variant (Pro 12Ala PPAR-gamma-2) may cause a blunted response to these drugs. Subjects with impaired glucose tolerance (a precursor of diabetes) will be recruited and treated with rosiglitazone, a thiazolidinedione. Insulin sensitivity will be tested before and after a 12 week treatment with rosiglitazone, both in terms of glucose uptake an inhibition of lipolysis (fat breakdown). Likewise, gene expression in fat and muscle will be studies before and after treatment. The protocol concludes with a 12 week didactic weight management program.