Abstract
ATP has been proposed to be co‐released with insulin to act as an autocrine signal in insulin secretion of pancreatic islets, but published data are inconclusive. Because human islet biology is unique, we measured both dynamic insulin release and cytoplasmic free Ca2+ concentration, [Ca2+]i, to investigate the functional role of purinergic receptors in human β cells. Activation of ionotropic (P2X) and metabotropic (P2Y) purinergic receptors increased insulin secretion. ATP elicited [Ca2+]i responses in β cells that were dependent on extracellular Ca2+, suggesting P2X receptor activation. Human β cells were immunoreactive for P2X2 and P2X3 receptors. To test the role of endogenously released ATP on glucose‐induced insulin release, we investigated the effect of P2 receptor antagonists. Suramin (P2 antagonist), isoPPADS and oxidized ATP (P2X antagonists) reduced insulin release by 40%, 30%, and 65%, respectively. Reactive blue 2 (P2Y antagonist) had no effect. Glucose‐induced insulin release was decreased by apyrase, an enzyme that degrades extracellular ATP. We conclude that ATP is a positive autocrine signal for insulin secretion in human pancreatic β‐cells. Autocrine signaling may thus be a prerequisite for a functional endocrine pancreas, allowing for adequate hormone release under physiological conditions where blood glucose concentration is only modestly changed.
Supported by JDRF and DRIF