Studies on mechanisms involved in hypoglycemia-induced platelet activation.
The aim of our study was to investigate the mechanisms involved in hypoglycemia-induced platelet activation. Sixteen healthy male subjects received a 60-min intravenous infusion of human regular insulin at the rate of 64 mU . m-2 . min-1: throughout 150 min, we serially measured plasma concentrations of glucose, insulin, and counterregulatory hormones; platelet sensitivity to ADP, thrombin and platelet-activating factor; plasma concentrations of platelet markers for specific proteins of in vivo release reaction (beta-thromboglobulin and platelet factor 4). Our study showed that insulin-induced hypoglycemia causes a significant increase in platelet sensitivity to aggregating agents in vitro and a platelet release reaction in vivo. Hypoglycemia-induced platelet activation was not correlated with plasma glucose concentrations at nadir and occurred before the increase of plasma growth hormone and cortisol. To further elucidate the mechanisms of hypoglycemia-induced platelet activation, we incubated in vitro platelet-rich plasma (PRP) of seven fasting healthy subjects with the same concentrations of insulin, epinephrine, glucagon, growth hormone, and cortisol measured in vivo during insulin-induced hypoglycemia. Only epinephrine was able to increase platelet sensitivity to aggregating agents. To investigate the role of alpha-adrenergic receptors in this phenomenon, we also studied four healthy subjects on another occasion, repeating the above-described insulin infusion together with intravenous infusion of phentolamine (-15 to +150 min), 5 mg over 2 min followed by 500 micrograms/min. alpha-Blockade was able to suppress hypoglycemia-induced increase of platelet sensitivity to aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000032:analysis; D001620:beta-Thromboglobulin / Q000378:metabolism
D006728:Hormones; D007328:Insulin; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4; D013006:Growth Hormone; D005934:Glucagon; D006854:Hydrocortisone; D004837:Epinephrine