Polymorphonuclear neutrophils (PMN) are able to destroy invasive mircoorganisms by a wide variety of functions. Whereas insulin does not stimulate hexose transport in PMN, previous reports have clearly shown that this hormone regulates glucose metabolism inside this cell, raising the question of insulin action on PMN functions in humans. It is interesting that in vitro studies established a strong relationship between specific binding of insulin to its PMN membrane receptor and the activation of the main PMN functions. Therefore, investigation in healthy subjects under strict euglycemia and physiological insulinemia was performed to understand the in vivo-specific action of insulin on PMN functions without hyperglycemia interferences. We determined numerous PMN functions before and after hyperinsulinemia (0.5 mU/kg/min) and euglycemia (0.9 g/l) clamp for 4 h in eight adult healthy volunteers (24+/-6 years). The total number of PMN and the number of PMN expressing CD11b, CD15, CD62L, and CD89 were significantly increased over baseline (P<0.001), whereas the density of these receptors was down-regulated (P<0.01) by insulin. PMN chemotaxis (+117%, P<0.05), phagocytosis (+29%, P<0.001), and bactericidal (+17-25%, P<0.001) capacities were increased during the insulin clamp (P<0.05). Therefore, insulin treatment may modulate PMN functions not only by attainment of a better metabolic control, as suggested by in vivo studies in diabetic patients, but also through a direct effect of insulin.