Desensitization of the platelet aggregation response to adrenaline during insulin-induced hypoglycaemia in man.
The aim of the present study was to investigate the influence of insulin-induced hypoglycaemia on platelet sensitivity to adrenaline and non-adrenergic agonists in man. Twenty-five healthy male subjects volunteered for the study. To evaluate the effects on platelets of different insulin-adrenaline interrelationships, two experimental models were used. In the first, hypoglycaemia was induced by a 60-min IV infusion of human insulin at the rate of 64 mU m-2 min-1, whereas in the other the same insulin dose was administered as an IV bolus (3.84 U m-2). Throughout the studies, plasma glucose, insulin, and adrenaline were measured together with platelet sensitivity to adrenaline, ADP, platelet activating factor, collagen, and sodium arachidonate. In both studies, hypoglycaemia induced a reduction of platelet sensitivity to adrenaline (p = 0.006 in infusion and p = 0.045 in injection study). In particular, maximal aggregation to adrenaline fell from 47.9 +/- 9.9 (+/- SE) to 31.1 +/- 11.3% at the hypoglycaemic nadir in the infusion study, and from 64.6 +/- 8.2 to 34.6 +/- 10.3% at the hypoglycaemic nadir in the injection study. In the injection study an increase of platelet sensitivity to ADP (p = 0.05), platelet activating factor (p = 0.018), sodium arachidonate (p = 0.035), and collagen (p = 0.027) was also found, in agreement with observations already published using the infusion protocol. Thus, insulin-induced hypoglycaemia increases platelet sensitivity to non-adrenergic agonists and decreases platelet response to adrenaline.
Trovati
M
M
Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Italy.
Anfossi
G
G
Mularoni
E
E
Massucco
P
P
Cavalot
F
F
Mattiello
L
L
Emanuelli
G
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D061389:Insulin, Regular, Pork; D007700:Kinetics; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D061389:Insulin, Regular, Pork; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D000244:Adenosine Diphosphate; C000006:insulin, neutral; D004837:Epinephrine