Modulation of insulin sensitivity by adenosine. Effects on glucose transport, lipid synthesis, and insulin receptors of the adipocyte.

Insulin action and insulin binding in isolated rat fat cells incubated with adenosine or adenosine deaminase were studied. Adenosine enhanced the effects of insulin on glucose transport and glucose metabolism. The nucleoside shifted the concentration-response curves of insulin-stimulated D-[3-3H]glucose incorporation into total lipids, and of D-[U-14C]glucose conversion to fatty acids to smaller insulin concentrations. In addition, the maximal response of the fatty acid synthesis was increased. Insulin sensitivity and maximal response to insulin of the glucose transport system, as assessed by the rate of uptake of 2-deoxyglucose and 3-O-methylglucose, were increased by adenosine. The adenosine derivative N6-phenylisopropyladenosine similarly enhanced deoxyglucose transport in the presence of insulin. However, insulin binding was not affected by adenosine. The results suggest that adenosine modulates insulin action at a step distal from the insulin receptor, and before, or at, the glucose transport system.