*Controversies in Platelet Functions in Diabetes Mellitus Type 1 DOI: http://dx.doi.org/10.5772/intechopen.108276*

P-selectin as well as fibrinogen binding, in addition to PRP aggregation. These effects are independent of extracellular calcium and glucose [115]. Insulin, both at physiological and supranormal levels, enhances platelet P-selectin, fibrinogen binding, and platelet-leukocyte aggregates in whole blood [115, 116]. Insulin at low doses decreases platelet aggregation, while at high doses enhances platelet aggregation due to the paradoxical changes in intraplatelet cGMP levels [114].

Whereas low-dose insulin decreases platelet aggregation, high dose increases platelet aggregation in vitro [115, 117]. These effects are mediated by paradoxical changes in intraplatelet cGMP levels [116] and co-operativity with insulin-like growth factor on platelets [118]. Indeed platelets pose few insulin receptors and responses are weak but potentiated by IGF-1 [118] in the presence of extracellular calcium [119]. This is because insulin and IGF-1 circulate together and share a lot of similarities in both structure and receptors [120, 121]. Thus, at high insulin concentrations, the effects of IGF-1 predominate, thus explaining the increased platelet aggregation and response to agonists in patients on hyperinsulinemia.

In healthy, non-diabetic non-obese subjects, insulin decreases platelet adherence to collagen surfaces, decreases agonist-induced (ADP, collagen, AA, and TRAP) platelet aggregation but increases intracellular cGMP. These responses are abolished or blunted in obese individuals [122].
