Role of adenosine in regulation of carbohydrate metabolism in contracting muscle.

Adenosine production from AMP in the sarcoplasm and interstitial space of muscle is markedly enhanced during contractions. The produced adenosine may act as a 'local hormone' by binding to various types of adenosine receptors present in the membrane of adjacent cells, including skeletal muscle, vascular smooth muscle and neurons. Thus, interstitial adenosine may significantly contribute to regulation of muscle carbohydrate metabolism, both by adjusting metabolism and local blood flow to the energy needs imposed by a given degree of contratile activity on the muscle cell. The studies presented here demonstrate that endogenous adenosine via A1-adenosine receptors is able to directly stimulate insulin-mediated glucose transport in oxidative muscle cells during contractions. In addition, adenosine may further contribute to stimulation of muscle glucose uptake during contractions by increasing blood flow and thereby targetting glucose and insulin delivery to active muscle fibres. Furthermore, our findings demonstrate that adenosine via A1- and A2-receptors may inhibit glycogen breakdown in oxidative muscle tissue which during contractions is simultaneously exposed to insulin and beta-adrenergic stimulation. It is concluded that adenosine importantly contributes to regulation of carbohydrate metabolism in oxidative muscle fibers during contractions.