Comparison between the effects of the rapid recombinant insulin analog aspart and those of human regular insulin on platelet cyclic nucleotides and aggregation

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 NG-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. (C) 2002 Elsevier Science Ltd. All rights reserved.