Enhancing effect of advanced glycation end products on serotonin-induced platelet aggregation in patients with diabetes mellitus

Abstract

Advanced glycation end products (AGEs) are thought to be responsible for some complications of diabetes mellitus (DM), including microangiopathy. Plasma serotonin is increased in diabetes mellitus patients, and this increase is related, at least in part, to platelet hyperfunction. In order to clarify the relationship between advanced glycation end products, serotonin, and thrombotic complications in diabetes mellitus patients, we examined the effect of advanced glycation end products on serotonin-induced platelet aggregation. In diabetic patients, although serotonin-induced platelet aggregation was enhanced with an increase in serum-advanced glycation end products, there was no correlation between platelet aggregation and either hemoglobin A1c or fasting blood sugar. To examine the direct effect of advanced glycation end products on platelet aggregation, we prepared advanced glycation end products by in vitro incubation of human albumin with glucose (250 mM) at 37 °C for 8 weeks. Serotonin-induced platelet aggregation was dose-dependently increased by advanced glycation end products. Adenosine diphosphate-induced platelet aggregation also was increased by advanced glycation end products, but this increment was diminished by addition of sarpogrelate, a selective serotonin receptor antagonist. These results suggest that advanced glycation end products enhance platelet aggregation through the serotonin receptor, and perhaps influencing the development of thrombotic complications in diabetic patients.