ADENOSINE EFFECTS UPON INSULIN ACTION ON LIPOLYSIS AND GLUCOSE-TRANSPORT IN HUMAN ADIPOCYTES

The dose response effect of a new adenosine analogue, GR79236 (N-[1S t rans-2-hydroxycyclopentyl] adenosine) upon insulin sensitivity was exa mined in human adipocytes. The influence of adenosine upon insulin sen sitivity for suppression of lipolysis and stimulation of glucose trans port was examined. Removal of adenosine by use of adenosine deaminase stimulated lipolysis to the same extent as did 10(-9) M noradrenaline. GR79236 brought about dose dependent inhibition of lipolysis with hal f-maximal effect at 11.3 +/- 7.8 x 10(-9) M. When lipolysis was stimul ated by noradrenaline alone the subsequent inhibition of lipolysis bro ught about by GR79236 was significantly greater than that of insulin. To examine adenosine effects on the insulin signalling pathway separat ely from those on lipolysis, the insulin sensitivity of glucose transp ort was examined. Removal of adenosine brought about a small but signi ficant increase in the concentration of insulin required for half-maxi mal stimulation of glucose transport. Adenosine agonists offer promise as new agents for the modulation of metabolism in diabetes and other states of insulin resistance.