PHARMACOGENETICS OF PRO 12ALA PPAR-GAMMA-2

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。本方案的目的是确定为什么有些人对噻唑烷二酮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而起作用。受试者将根据他们的基因型被招募，因为据信，一种特定的变异（Pro 12Ala ppar - γ -2）可能导致对这些药物的反应迟钝。葡萄糖耐量受损（糖尿病的前兆）的受试者将被招募并使用罗格列酮（一种噻唑烷二酮）治疗。胰岛素敏感性将在罗格列酮治疗12周前后进行测试，包括葡萄糖摄取和脂肪分解（脂肪分解）的抑制。同样，脂肪和肌肉的基因表达也将在治疗前后进行研究。该方案以12周的说教式体重管理计划结束。

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.