Platelet and monocyte activation by hyperglycemia and hyperinsulinemia in healthy subjects.
Type 2 diabetes mellitus (T2DM) patients have hyperglycemia and hyperinsulinemia and increased risk of atherosclerosis and acute vascular complications. We have reported elevated circulating tissue factor procoagulant activity (TF-PCA) during hyperglycemia (HG) and hyperinsulinemia (HI) in normal subjects. To evaluate the effect of hyperglycemia and hyperinsulinemia on blood cell activation, we assessed platelet CD40L and P-selectin, monocyte tissue factor (TF), and the formation of monocyte-platelet and neutrophil-platelet aggregates. These were assessed in the resting state and following activation with ADP and thrombin (SFLLRN). Healthy individuals were subjected to 24 h of hyperglycemia and hyperinsulinemia, selective hyperglycemia, selective hyperinsulinemia, or normal glucose and insulin. Platelet CD40L expression increased with high glucose/high insulin, selective hyperglycemia and selective hyperinsulinemia. Monocyte-platelet aggregates increased with high glucose/high insulin. Monocyte TF expression increased with high glucose/high insulin and with selective hyperinsulinemia. Upon stimulation with ADP and SFLLRN, monocyte-platelet and neutrophil-platelet aggregates, platelet CD40L and P-selectin, and monocyte TF increased compared to the resting state but was not different between 0 and 24 h, indicating that the responsiveness to those agonists was not altered.


CONCLUSIONS
Hyperglycemia-hyperinsulinemia in healthy individuals induced platelet activation and monocyte TF expression promoting a procoagulant and proinflammatory state that may contribute to acute vascular events and atherogenesis. Platelet responsiveness to activation with ADP or SFLLRN appears not to be altered by hyperglycemia-hyperinsulinemia.
Vaidyula
Vijender R
VR
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Boden
Guenther
G
Rao
A Koneti
AK
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis; D048909:Diabetes Complications / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000209:etiology; D006946:Hyperinsulinism / Q000097:blood*; D007249:Inflammation / Q000097:blood / Q000209:etiology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects
D001798:Blood Proteins; D010446:Peptide Fragments; C082835:thrombin receptor peptide (42-47); D000244:Adenosine Diphosphate