Stimulation of insulin secretion and improvement of glucose tolerance in rat and dog by the P 2y ‐purinoceptor agonist, adenosine‐5′‐O‐(2‐thiodiphosphate)

1 In vivo effect of a P 2y ‐purinoceptor agonist, adenosine‐5′‐O‐(2‐thiodiphosphate) (ADPβS), on insulin secretion and glycaemia were studied both in rats and dogs. 2 In anaesthetized rats, i.v. administered ADPβS (0.2 mg kg −1 ) produced an insulin response dependent on the nutritional state of the animals, since we observed only a transient increase in overnight‐fasted rats and a sustained insulin secretion followed by a reduction in plasma glucose levels in fed rats. During an i.v. glucose tolerance test, ADPβS enhanced insulin release and thus increased the glucose disappearance rate. 3 In anaesthetized fasted dogs, i.v. administered ADPβS (0.1 mg kg −1 ) increased pancreaticoduodenal insulin output and slightly decreased blood glucose levels. 4 In conscious fasted dogs, orally administered ADPβS (0.1 mg kg −1 ) transiently increased insulinemia and punctually reduced glycaemia. Furthermore, during an oral glucose tolerance test, orally administered ADPβS at the same dose markedly enhanced insulin secretion and consequently reduced the hyperglycaemia. 5 In conclusion, the P 2y ‐agonist, ADPβS, is a potent insulin secretagogue in vivo , improves glucose tolerance and is effective after oral administration. Thus, the P 2y ‐purinoceptors of the β cell may be a target for new antidiabetic drugs.