، در شرايط برون تني و درون تني PDE3 مقايسه بين اثرات انسولينوتروپيك ميلرينون و آمرينون ، مهاركننده هاي انتخابي

Comparison between the insulinotropic effects of milrinone and amrinone,selective PDE3 inhibitors in in-vitro and in-vivo conditions

In the present study, the effects of milrinone and amrinone, selective PDE3 inhibitors, on insulin secretion have been investigated, using in-vitro static (incubation of rat islets and CRl- D2 cultured insulin secreting cells) and dynamic methods (islets perifusion) and in-vivo procedures. In incubation of the islets, 10mM of glucose increased the insulin secretion and 10^-4M milrinone augmented glucose- induced insulin secretion significantly (P<0.05). But the effect of amrinone, another selective PDE3 inhibitor, was not significant. Milrinone increased 10 mM glucose induced insulin secretion in a dose-dependent manner (EC50 = 9 (Mio)M). However, in the same conditions, the different concentration of amrinone did not produce a significant effect. In the presence of 3mM glucose, the amount of insulin which was released by CRI-D2 cells was very low and 10mM glucose did not increase insulin secretion significantly. But addition of 10^-4 M milrinone to 10mM glucose increased the amount of insulin release. In in-vivo experiments, milrinone increased plasma insulin concentration in a dose dependent manner (P<0.05). While amrinone, with the same concentrations, not only failed to increase insulin secretion, but it seemed to have a decreasing effect, although the effects were not significant (p>0.05). Considering the differences between milrinone and amrinone IC50 for PDE3 activity inhibition in other publications, we may conclude that the difference between the effects of milrinone and amrinone on insulin secretion is because of their 1C50. The effects of milrinone confirm the insulinotropic effect of selective PDE3 inhibitor drugs. In comparison with the milrinone effects, the different effect of amrinone might be because of variations in PDE inhibitor effects among different tissues (tissue specificity) or existence of other mechanisms in augmentation of glucose-induced insulin release by selective PDE3 inhibitors.