PMID- 17127486 OWN - NLM STAT- MEDLINE DCOM- 20070202 LR - 20161019 IS - 0953-7104 (Print) IS - 0953-7104 (Linking) VI - 17 IP - 8 DP - 2006 Dec TI - Platelet and monocyte activation by hyperglycemia and hyperinsulinemia in healthy subjects. PG - 577-85 AB - 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. FAU - Vaidyula, Vijender R AU - Vaidyula VR AD - Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA. FAU - Boden, Guenther AU - Boden G FAU - Rao, A Koneti AU - Rao AK LA - eng GR - R01 DK058895/DK/NIDDK NIH HHS/United States GR - R01-DK58895/DK/NIDDK NIH HHS/United States PT - Clinical Trial PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - Platelets JT - Platelets JID - 9208117 RN - 0 (Blood Proteins) RN - 0 (Peptide Fragments) RN - 0 (thrombin receptor peptide (42-47)) RN - 61D2G4IYVH (Adenosine Diphosphate) SB - IM MH - Adenosine Diphosphate/pharmacology MH - Adult MH - Atherosclerosis/blood/etiology MH - Blood Platelets/*metabolism MH - Blood Proteins/analysis MH - Diabetes Complications/blood MH - Diabetes Mellitus, Type 2/blood MH - Female MH - Humans MH - Hyperglycemia/*blood/etiology MH - Hyperinsulinism/*blood MH - Inflammation/blood/etiology MH - *Macrophage Activation/drug effects MH - Male MH - Monocytes/*metabolism MH - Peptide Fragments/pharmacology MH - *Platelet Aggregation/drug effects EDAT- 2006/11/28 09:00 MHDA- 2007/02/03 09:00 CRDT- 2006/11/28 09:00 PHST- 2006/11/28 09:00 [pubmed] PHST- 2007/02/03 09:00 [medline] PHST- 2006/11/28 09:00 [entrez] AID - X684U5855L334HP7 [pii] AID - 10.1080/09537100600760814 [doi] PST - ppublish SO - Platelets. 2006 Dec;17(8):577-85. doi: 10.1080/09537100600760814.