The mechanism behind the cardioprotective effect of remote preconditioning is incompletely understood. Data from experimental studies suggest that a combination of humoral and neurogenic factors mediate the transition of protective signals from peripheral tissues to the myocardium. A major break-through in the understanding of the signaling was the observation that vagal nerve activation is involved. Key signaling pathways in the target organ are likely to be mediated via the vascular endothelium which is known to play an important role during the early reperfusion period. Thus, animal studies have demonstrated that RIPC stimulates endothelial nitric oxide production secondary to down-regulation of arginase. It remains unclear, however, whether RIPC via activation of endothelial nitric oxide preserves endothelial function in humans. Additional data indicate strongly that glucagon-like peptide-1 (GLP-1) provides protection against ischemia-reperfusion injury in experimental animals models as well as in clinical studies. The role of GLP-1 in the protective effect of RIPC has previously not been investigated, however. The present study was therefore designed to determine the involvement of GLP-1 in the protection induced by RIPC via endothelial activation in humans. To this end we use a model of reversible ischemia-reperfusion injury in the forearm, and the GLP-1 antagonist exendin 9-39 (Ex 9-39).