Effects of Adenosine A(1) Receptor Antagonism on Lipogenesis and Lipolysis in Isolated Rat Adipocytes

摘要

Adenosine is secreted from adipocytes, binds to adenosine A(1) receptor and modulates various functions of these cells. In the present study, the effects of an adenosine A(1) receptor antagonist ( DPCPX; 0.01, 0.1 and 1 mu M) on lipogenesis, glucose transport, lipolysis and the antilipolytic action of insulin were tested in rat adipocytes. DPCPX had a very weak effect on lipogenesis and did not significantly affect glucose uptake. In adipocytes incubated with 1 mu M DPCPX, lipolysis increased. This effect was blunted by insulin and by a direct inhibitor of protein kinase A. Moreover, 0.1 mu M DPCPX substantially enhanced the lipolytic response to epinephrine and increased cAMP in adipocytes. However, DPCPX was ineffective when lipolysis was stimulated by direct activation of protein kinase A. Adipocyte exposure to epinephrine and insulin with or without 0.1 mu M DPCPX demonstrated that this antagonist increased the release of glycerol. However, despite the presence of DPCPX, insulin was able to reduce lipolysis. It is concluded that DPCPX had a weak effect on lipogenesis, whereas lipolysis was significantly affected. The partial antagonism of adenosine A(1) receptor increased lipolysis in cells incubated with epinephrine alone and epinephrine with insulin due to the synergistic action of 0.1 mu M DPCPX and epinephrine.