MECHANISM OF INSULIN SENSITIZING EFFECT OF PIOGLITAZONE-ROLE OF ADIPONECTIN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。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 研究中心，而研究中心不一定是研究者所在的机构。 目的：研究脂联素及其受体在吡格列酮胰岛素增敏作用中的作用。 研究报告：这是一项开放标签研究，旨在评价吡格列酮对2型糖尿病、糖耐量受损、肥胖非糖尿病受试者和瘦型健康对照的骨骼肌和脂肪组织受试者中葡萄糖、游离脂肪酸/脂质代谢和脂肪细胞因子（特别是脂联素水平及其基因表达）的作用机制。 每组15例受试者将接受吡格列酮45 mg治疗16周，并将在吡格列酮治疗前后参加4项不同的研究。 方法：每例受试者将参加1）口服葡萄糖耐量试验，2）高胰岛素正葡萄糖钳夹联合示踪剂研究（用于肝葡萄糖生成和热量测定以及骨骼肌活检），3）脂肪组织活检，以及4）MRI研究（用于测量肌细胞内和肌细胞外脂肪）。 临床相关性：这项研究将有助于了解脂联素及其受体在吡格列酮胰岛素增敏作用中的作用，以及该药物是否在有糖尿病风险的受试者中具有类似的有益作用。

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. OBJECTIVE: To study the role of adiponectin and its receptors in the insulin sensitizing effect of pioglitazone. RESEARCH PLAN: This is an open label study to evaluate the mechanism of action of pioglitazone on glucose, free fatty acid/lipid metabolism, and adipocytokines, particularly adiponectin levels and its gene expression in skeletal muscle and adipose tissue subjects with type 2 diabetes, impaired glucose tolerance, obese non diabetic subjects and lean healthy controls. Fifteen subjects in each group will receive Pioglitazone 45mg for 16 weeks and will participate in four different studies before and after pioglitazone treatment. METHODS: Each subject will participate in 1) oral glucose tolerance test, 2) hyperinsulinemic euglycemic clamp combined with tracer studies for hepatic glucose production and calorimetry and skeletal muscle biopsy, 3) adipose tissue biopsy, and 4) MRI studies for measurement of intramyocellular and extramyocellular fat. CLINICAL RELEVANCE: This study will help understand the role of adiponectin and its receptors in the insulin sensitizing effect of Pioglitazone and whether this drug has similar beneficial effects in subjects who are at risk of developing diabetes.