In vivo evidences that insulin regulates human polymorphonuclear neutrophil functions

Polymorphonuclear neutrophils (PMN) are able to destroy invasive mircoorganisms by a wide variety of functions. Whereas insulin does not stimulate hexose transport in PAIN, previous reports have clearly shown that this hormone regulates glucose metabolism inside this cell, raising the question of insulin action on PAIN functions in humans. It is interesting that in vitro studies established a strong relationship between specific binding of insulin to its PAIN membrane receptor and the activation of the main PAIN functions. Therefore, investigation in healthy subjects under strict euglycemia and physiological insulinemia was performed to understand the in vivo-specific action of insulin on PAIN functions without hyperglycemia interferences. We determined numerous PAIN 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 PAIN and the number of PAIN 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. PAIN 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 PAIN 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.