P 2y purinoceptor responses of β cells and vascular bed are preserved in diabetic rat pancreas

1 To investigate the effect of experimental diabetes on the P 2y purinoceptor responses of pancreatic β‐cells and vascular bed, we used adenosine‐5′‐O‐(2‐thiodiphosphate) (ADPβS), a potent and stable P 2y agonist. This work was performed in the isolated perfused pancreas of the rat. 2 Diabetes was induced by streptozotocin (66 mg kg −1 , i.p.). Five weeks after the induction of diabetes, on the day of pancreas isolation, the animals displayed marked hyperglycaemia (37.6 ± 2.7 m m ). Age‐matched rats were used as controls. 3 Insulin response to a glucose stimulation from 5 to 10 m m was completely lost and stimulation of insulin release by the sulphonylurea, tolbutamide (185 μ m ), was drastically impaired in the diabetic pancreas (maximum responses were 1.5 ± 0.4 and 7.0 ± 1.4 ng min −1 for diabetic and age‐matched rats respectively). 4 In contrast, in the diabetic pancreas ADPβS (15 μ m ), infused in the presence of glucose 5 m m , elicited an immediate and significant insulin release similar to that observed in the age‐matched pancreas (maximum responses were 7.6 ± 1.5 and 6.7 ± 1.3 ng min −1 respectively). This ADPβS stimulating effect occurred independently of the glucose concentration (5, 8.3 and 28 m m ) in the diabetic pancreas. On pancreatic vascular resistance, ADPβS induced a similar vasodilatation in diabetic and age‐matched rats. 5 In conclusion, ADPβS retains its insulin stimulatory and vasodilator effects in experimental diabetes; P 2y purinoceptors could therefore be considered as a new target for the development of antidiabetic drugs.