Although P2 receptors for adenosine 5-triphosphate (ATP) and/or adenosine 5-diphosphate (ADP) have been characterized in mammalian pancreatic β cells, no evidence for an insulin-secreting effect of P2 receptor agonists has been reported as yet in humans. The present study aimed at investigating whether P2 receptor agonists could stimulate insulin release in human pancreatic islets obtained from brain-dead organ donors. Experiments were performed using different glucose concentrations and insulin was measured by radioimmunoassay. When the glucose concentration (8.3 mmol/L) was slightly stimulating for insulin release, α, β-methylene ATP (200 μmol/L) and ADPβS (50 μmol/L) similarly amplified insulin secretion: both compounds induced a threefold increase in insulin response. In the presence of a nonstimulating glucose concentration (3.0 mmol/L), only α, β-methylene ATP could induce a significant 1.4-fold increase in insulin release, ADPβS being completely ineffective. These results give evidence that P2 receptor agonists are effective in stimulating insulin release in humans, the effect of the P2Y agonist being essentially glucose dependent.