INHIBITION OF PLATELET-AGGREGATION AND THE STIMULATION OF PROSTACYCLIN SYNTHESIS BY INSULIN IN HUMANS

An intravenous bolus injection of insulin (35.5 muM) followed by an in fusion of insulin (0.53 muM . kg-1 . h-1) for 2.5 h (which maintained plasma levels between 0.71 nM to 1.4 nM) in normal fasting volunteers (n = 16), increased [H-3]prostaglandin E1 (a probe for prostacyclin) b inding to platelets by two- to threefold over the control. Scatchard a nalyses showed that the increased binding was due to the increase of b oth high and low affinity receptor numbers with little change in the r eceptor affinities. Similar results were obtained by using [H-3]prosta cyclin as the radioligand. The increased binding was associated with m ore than a twofold decrease of the minimum concentration of prostanoid needed to inhibit aggregation of platelets through the increased form ation of adenosine 3',5'-cyclic monophosphate. Furthermore, the infusi on increased the mean plasma prostacyclin level from 12.10 +/- 4.5 pM to 23.9 +/- 6.7 pM (n = 16; P < 0.001). These effects of insulin were at least partially direct, since the treatment of endothelial cells wi th insulin in tissue culture stimulated the production of the autacoid . Bolus injection of insulin (0.71 muM/kg) showed that the above effec ts of insulin could be demonstrated within 20 min after the injection, attained maximal ranges in approximately 60 min, and disappeared by 2 -4 h.