INS and Insulin resistance: Several previous studies suggested that insulin resistance of megakaryocytes/platelets is the underlying cause of the platelet hyperactivity observed in patients with insulin resistance.17,18 Here, we demonstrate that deletion of IR, using IRflox/flox; Pf4-Cre mice, did not increase platelet activation in response to either the PAR-4 agonist PAR4-AP or GPVI agonist CRP-XL.