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


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.
Russo
Isabella
I
Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, 10043 Orbassano, Turin, Italy.
Massucco
Paola
P
Mattiello
Luigi
L
Cavalot
Franco
F
Anfossi
Giovanni
G
Trovati
Mariella
M
D000328:Adult; D001792:Blood Platelets / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000031:analogs & derivatives / Q000494:pharmacology*; D061267:Insulin Aspart; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009712:Nucleotides, Cyclic / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D009712:Nucleotides, Cyclic; D011994:Recombinant Proteins; D009569:Nitric Oxide; D061267:Insulin Aspart; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D006152:Cyclic GMP