P2 receptor agonists stimulate insulin release from human pancreatic islets

Although P2 receptors for adenosine 5'-triphosphate (ATP) and/or adenosine 5'-diphosphate (ADP) have been characterized in mammalian pancreatic beta c ells, no evidence for an insulin-secreting effect of P2 receptor agonists h as been reported as yet in humans. The:present study aimed at investigating whether P2 receptor agonists could stimulate insulin release in human panc reatic islets obtained from brain-dead organ donors. Experiments were perfo rmed using different glucose concentrations and insulin was measured by rad ioimmunoassay. When the glucose concentration (8.3 mmol/L) was slightly sti mulating for insulin release, alpha,beta -methylene ATP (200 mu mol/L) and ADP betaS (50 mu mol/L) similarly amplified insulin secretion: both compoun ds induced a threefold increase in insulin response. In the presence of a n onstimulating glucose concentration (3.0 mmol/L), only alpha,beta -methylen e ATP could induce a significant 1.4-fold increase in insulin release, ADP betaS being completely ineffective. These results give evidence that P2 rec eptor agonists are effective in stimulating insulin release in humans, the effect of the P2Y agonist being essentially glucose dependent.