Inhibition of Platelet-Collagen Interaction

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Abstract
Insulin resistance is associated with an increased risk of atherothrombotic vascular disease, but the mechanisms are poorly understood. We determined how insulin in vivo regulates platelet activation in nonobese and obese subjects by using methods mimicking thrombus formation. Twelve nonobese (aged 42±2 years, body mass index 24.0±0.4 kg/m2) and 14 obese (aged 43±1 years, body mass index 37.2±1.5 kg/m2) subjects were studied under euglycemic hyperinsulinemic (3-hour insulin infusion of 1 mU · kg−1 · min−1) conditions. Before and at the end of hyperinsulinemia, the following were determined: (1) platelet-related early hemostasis (shear rate of ≈4000 s−1) by platelet function analysis; (2) platelet deposition to collagen during whole-blood perfusion (shear rate of 1600 s−1); (3) aggregation responses to collagen, thrombin receptor-activating peptide, ADP, and epinephrine; and (4) platelet cGMP concentrations. Insulin action on glucose metabolism was 69% lower in the obese subjects (1.6±0.2 mg · kg−1 · min−1...