Inhibition of platelet aggregation and the stimulation of prostacyclin synthesis by insulin in humans.
An intravenous bolus injection of insulin (35.5 microM) followed by an infusion of insulin (0.53 microM.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 [3H]prostaglandin E1 (a probe for prostacyclin) binding to platelets by two- to threefold over the control. Scatchard analyses showed that the increased binding was due to the increase of both high and low affinity receptor numbers with little change in the receptor affinities. Similar results were obtained by using [3H]prostacyclin as the radioligand. The increased binding was associated with more than a twofold decrease of the minimum concentration of prostanoid needed to inhibit aggregation of platelets through the increased formation of adenosine 3',5'-cyclic monophosphate. Furthermore, the infusion 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 with insulin in tissue culture stimulated the production of the autacoid. Bolus injection of insulin (0.71 microM/kg) showed that the above effects of insulin could be demonstrated within 20 min after the injection, attained maximal ranges in approximately 60 min, and disappeared by 2-4 h.
Kahn
N N
NN
Department of Medicine, Mount Sinai Medical Center, New York 10029.
Bauman
W A
WA
Hatcher
V B
VB
Sinha
A K
AK
D000328:Adult; D000527:Alprostadil / Q000378:metabolism / Q000494:pharmacology; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D004573:Electrolytes / Q000097:blood; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism
D004573:Electrolytes; D007328:Insulin; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil