A1 adenosine receptor antagonism improves glucose tolerance in
zucker rats.
Xu, Baiyang, Deborah A. Berkich, George H. Crist, and Kathryn F.
Lanoue.
Kathryn F. LaNoue, Ph.D., Professor, Department of Cellular and
Molecular Physiology, The Milton S. Hershey Medical Center, The
Pennsylvania State University, College of Medicine, 500 University
Drive, Hershey, PA 17033-0850
APStracts 4:0248E, 1997.
The A1-adenosine receptor (A1ar) antagonist, BW1433, was administered
to lean and obese Zucker rats to probe the influence of endogenously
activated A1ars on whole body energy metabolism. The drug induced a
transient increase in lipolysis as indicated by a rise in serum
glycerol in obese rats. The disappearance of the response by day 7 of
chronic studies was accompanied by an increase in A1ar numbers.
Glucose tolerance tests were administered to rats treated with
BW1433. Peak serum insulin levels and areas under glucose curves
(AUGOs) were 34% and 41% lower respectively than controls in treated
obese animals and 19% and 39% lower in lean animals. With chronic
administration (6 weeks) AUGOs decreased 47% and 33% in obese and
lean animals, respectively. There was no effect of BW1433 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
lower levels of insulin.
Received 25 June 1997; accepted in final form 6 November 1997.
APS Manuscript Number E295-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 14 November 1997