ROLE OF A1 ADENOSINE RECEPTORS IN INSULIN RESISTANCE OF THE OBESE

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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.