The insulin-induced increase of guanosine-3',5'-cyclic monophosphate in human platelets is mediated by nitric oxide

• Published in: Diabetes (New York, N.Y.) Vol. 45; no. 6; pp. 768 - 770
• Main Authors: Trovati, M., Massucco, P., Mattiello, L., Piretto, V., Cavalot, F., Mularoni, E., Anfossi, G.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01-06-1996
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.45.6.768

The insulin-induced increase of guanosine-3',5'-cyclic monophosphate in human platelets is mediated by nitric oxide.
M Trovati ,
P Massucco ,
L Mattiello ,
V Piretto ,
F Cavalot ,
E Mularoni and
G Anfossi
Department of Clinical and Biological Sciences of the University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
Abstract
To investigate whether the insulin-induced increase of guanosine-3',5'-cyclic monophosphate (cGMP) in human platelets is mediated
by nitric oxide or is influenced by the nitric oxide precursor L-arginine, we measured cGMP in platelet-rich plasma obtained
from healthy volunteers incubated for 3 min with human recombinant insulin (0, 240, 480, 960, and 1,920 pmol/l) both with
and without 1) a 20-min incubation with the nitric oxide-synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (50, 70, 100,
and 1,000 micromol/l; n = 5 for each dose) and 2) a 20-min incubation with the nitric oxide precursor L-arginine (300 micromol/l;
n = 6). In a first set of experiments, insulin induced a dose-dependent cGMP increase, from 9.8 +/- 0.8 to 45.6 +/- 5.5 pmol/10(9)
platelets (P = 0.0001); in the presence of 1 mmol/l L-NMMA, this increase was blunted, cGMP being 8.9 +/- 1.4 and 11.1 +/-
2.2 pmol/10(9) platelets at 0 and 1,920 pmol/l insulin, respectively (NS). In the experiments with 70 and 100 micromol/l L-NMMA,
the insulin effect on cGMP was inhibited, whereas 50 micromol/l L-NMMA did not blunt this insulin effect. In another set of
experiments carried out to investigate the effects of L-arginine, insulin induced a dose-dependent cGMP increase, from 23.6
+/- 6.9 to 59.0 +/- 12.0 pmol/10(9) platelets (P = 0.0001); with L-arginine, basal cGMP values increased to 35.5 +/- 6.6 pmol/10(9)
platelets (P = 0.05), and insulin maintained its ability to enhance dose-dependently cGMP values, which rose to 76.8 +/- 19.4
pmol/10(9) platelets (P = 0.003). This study carried out in human platelets demonstrates that the cGMP increase induced by
insulin, which accounts for the antiaggregating effect of the hormone, is mediated by nitric oxide.