A(1) ADENOSINE RECEPTOR ANTAGONISM IMPROVES GLUCOSE-TOLERANCE IN ZUCKER RATS

The A(1) adenosine receptor (A1ar) antagonist 1,3-dipropyl-8-(p-acryli c)-phenylxanthine (BW-1433) was administered to lean and obese Zucker rats to probe the influence of endogenously activated A1ars on whole b ody energy metabolism. The drug induced a transient increase in lipoly sis as indicated by a rise in serum glycerol in obese rats. The disapp earance of the response by day 7 of chronic studies was accompanied by an increase in Alar numbers. Glucose tolerance tests were administere d to rats treated with BW-1433. Peak serum insulin levels and areas un der glucose curves (AUGs) were 34 and 41% lower in treated obese anima ls than in controls, respectively, and 19 and 39% lower in lean animal s. With chronic administration (6 wk), AUGs decreased 47 and 33% in ob ese and lean animals, respectively. There was no effect of BW-1433 in either lean or obese rats on weight gain or percent body fat. Thus the major sustained influence of whole body A1ar antagonism in both lean and obese animals was an increase in whole body glucose tolerance at l ower levels of insulin.