ADIPOSE TISSUE MCP-1 AND MIF: RELATION TO GLUCOSE TOLERANCE, INSULIN ACTION

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。2型糖尿病在美国正在增加，部分原因是肥胖率在过去30年里攀升了30%。肥胖导致2型糖尿病及其并发症的确切途径尚不清楚。最近的研究表明，脂肪细胞分泌大量的激素和分子，可能直接或间接导致糖尿病及其并发症。在这个项目中，我们将研究其中的两个因素，MCP-1和MIF。我们将测量50名肥胖（通过DEXA扫描测量）和葡萄糖耐量的男性和女性的脂肪组织（在局部麻醉下从腹部皮肤下穿刺活检获得）和血液中的MCP-1和MIF。MCP-1和MIF将与口服糖耐量试验期间的葡萄糖和胰岛素水平、胰岛素分泌和作用（来自静脉糖耐量试验）的测量以及前臂血管的反应性有关。超重受试者将在6个月的减肥干预前后进行研究。我们还将通过研究吡格列酮（Actos）或格列美脲（Amaryl）治疗6个月前后的2型糖尿病患者，来评估糖尿病控制对MCP-1和MIF的影响。这项研究将帮助我们了解肥胖是如何导致2型糖尿病及其并发症的，并可能为诊断、预防和治疗提供新的方法。

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. Type 2 diabetes is increasing in the US, in part, because rates of obesity have climbed 30% over the last 3 decades. The precise ways in which obesity causes type 2 diabetes and its complications are not known. Recent research indicates that fat cells secrete a large number of hormones and molecules that may directly or indirectly cause diabetes and its complications. In this project, we will examine 2 of these factors, MCP-1 and MIF. We will measure MCP-1 and MIF in fat tissue (obtained by needle biopsy under local anesthesia from underneath the skin of the abdomen) and in blood in 50 men and women with a wide range of obesity (measured by DEXA scanning) and glucose tolerance. MCP-1 and MIF will be related to glucose and insulin levels during the oral glucose tolerance test, measures of insulin secretion and action (from the intravenous glucose tolerance test) and the reactivity of blood vessels in the forearm. Overweight subjects will be studied before and after a 6-month weight loss intervention. We will also assess the effect of diabetes control on MCP-1 and MIF by studying patients with type 2 diabetes before and after 6 months of treatment with either pioglitazone (Actos) or glimepiride (Amaryl). This research will help us understand how obesity leads to type 2 diabetes and its complications and may suggest new approaches to diagnosis, prevention and treatment.