Stimulatory effect of exogenous diadenosine tetraphosphate on insulin and glucagon secretion in the perfused rat pancreas

1 Diadenosine triphosphate (AP3A) and diadenosine tetraphosphate (AP4A) are released by various cells (e.g. platelets and chromaffin cells), and may a ct as extracellular messengers. In pancreatic B-cells, AP3A and AP4A are in hibitors of the ATP-regulated K+ channels, and glucose increases intracellu lar levels of both substances. 2 We have studied the effect of exogenous AP3A and AP4A on insulin and gluc agon secretion by the perfused rat pancreas. 3 AP3A did not significantly modify insulin or glucagon release, whereas AP 4A induced a prompt, short-lived insulin response (approximate to 4 fold hi gher than basal value; P < 0.05) in pancreases perfused at different glucos e concentrations (3.2, 5.5 or 9 mM). AP4A-induced insulin release was aboli shed by somatostatin and by diazoxide. These two substances share the capac ity to activate ATP-dependent K+ channels, suggesting that these channels a re a potential target for AP4A in the B-cell. 4 AP4A stimulated glucagon release at both 3.2 and 5.5 mM glucose. This eff ect was abolished by somatostatin. 5 The results suggest that extracellular AP4A may play a physiological role in the control of insulin and glucagon secretion.