Introduction: Insulin aspart is a rapid insulin analog used in clinical practice: aim of the present study is to evaluate in human platelets its influence on: (i). concentrations of guanosine 3':5'-cyclic monophosphate (cGMP) and adenosine 3':5'-cyclic monophosphate (cAMP), mediators of platelet anti-aggregation; (ii). platelet aggregation to adenosine-5 diphosphate.
Materials and methods: In human platelets, incubated with human regular insulin or with insulin aspart, we measured: (1). guanosine 3':5-cyclic monophosphate and adenosine 3':5'-cyclic monophosphate concentrations by radioimmunoassays, with and without nitric oxide synthase (NOS) inhibition by N(G)-monomethyl-L-arginine, and phosphatidylinositol-3-kinase inhibition by wortmannin; (ii). aggregation to adenosine-5 diphosphate by Born's method.
Results: (i). Human regular insulin and insulin aspart increased both cyclic nucleotides; (ii). these effects were dependent on nitric oxide, being inhibited by N(G)-monomethyl-L-arginine, and mediated by the phosphatidylinositol-3-kinase pathway of insulin signalling, being inhibited by wortmannin; (iii). the effects exerted by insulin aspart on both cyclic nucleotides (ANOVA, p=0.0001) were more prolonged than those exerted by regular insulin; (iv) like human regular insulin, insulin aspart significantly decreased platelet response to ADP (ANOVA, p=0.0001): after 60 min of incubation, the anti-aggregating effect exerted by insulin aspart was significantly greater than that exerted by human regular insulin (p=0.027).
Conclusions: The effects of insulin aspart on platelet cyclic nucleotides and aggregation show kinetic differences compared to those of human regular insulin, resulting in more prolonged effects.