ROLE OF A1 ADENOSINE RECEPTORS IN INSULIN RESISTANCE OF THE OBESE

这些研究的长期目标是了解肥胖高血压患者胰岛素抵抗的分子基础。尽管对这个问题进行了深入的研究，但肥胖和胰岛素抵抗之间联系的本质仍不清楚。本研究的第一个具体目的是发现一种A1腺苷拮抗剂茶啡碱是否能改善肥胖胰岛素抵抗个体的胰岛素敏感性。第二个目的是评估瘦和肥胖个体间质腺苷水平与胰岛素抵抗之间的相关性。第三个目的是评估肥胖糖尿病患者细胞外间隙可能的高水平腺苷的来源。一个来源可能是交感突触囊泡含有高水平的ATP，然后在细胞外空间分解成腺苷。为了实现这些目标，我们计划对肥胖者、减重超过50磅的前肥胖者和瘦对照者的肌肉进行微透析。

The long range goal of the proposed studies is to understand the molecular basis for insulin resistance frequently observed in obese hypertensive individuals. The nature of the connection between obesity and insulin resistance is unclear, despite intensive investigation of the problem. The first specific aim of this proposal is to find out whether an A1 Adenosine antagonist, theophilline improves insulin sensitivity in obese insulin-resistant individuals. A second aim is to evaluate the correlation between interstitial adenosine levels and insulin resistance in lean and obese individuals. The third aim is to evaluate the source of possible high levels of adenosine in the extracellular space of obese diabetic individuals. One source may be sympathetic synaptic vesicles that contain high levels of ATP that then break down to adenosine in the extracellular space. To accomplish these aims, we plan to microdialyze muscles of obese individuals, formerly obese individuals who have lost more than fifty pounds, and lean control individuals.